Discerning the Chemistry in Individual Organelles with Small-Molecule Fluorescent Probes.

Principle has it that even the most advanced super-resolution microscope would be futile in providing biological insight into subcellular matrices without well-designed fluorescent tags/probes. Developments in biology have increasingly been boosted by advances of chemistry, with one prominent example being small-molecule fluorescent probes that not only allow cellular-level imaging, but also subcellular imaging. A majority, if not all, of the chemical/biological events take place inside cellular organelles, and researchers have been shifting their attention towards these substructures with the help of fluorescence techniques. This Review summarizes the existing fluorescent probes that target chemical/biological events within a single organelle. More importantly, organelle-anchoring strategies are described and emphasized to inspire the design of new generations of fluorescent probes, before concluding with future prospects on the possible further development of chemical biology.

[1]  M. Dardalhon,et al.  A redox-sensitive yellow fluorescent protein sensor for monitoring nuclear glutathione redox dynamics. , 2015, Methods in molecular biology.

[2]  Guillem Ramis,et al.  Cell uptake and localization studies of squaramide based fluorescent probes. , 2014, Bioconjugate chemistry.

[3]  Heinrich Leonhardt,et al.  DNA labeling in living cells , 2005, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[4]  T. Yi,et al.  A highly sensitive ratiometric fluorescent probe for the detection of cytoplasmic and nuclear hydrogen peroxide. , 2014, Analytical chemistry.

[5]  Seok-Cheol Hong,et al.  Two-photon fluorescent turn-on probe for lipid rafts in live cell and tissue. , 2008, Journal of the American Chemical Society.

[6]  Xinjing Tang,et al.  Visualizing fluoride ion in mitochondria and lysosome of living cells and in living mice with positively charged ratiometric probes. , 2015, Analytical chemistry.

[7]  C. Che,et al.  Subcellular localization of a fluorescent artemisinin derivative to endoplasmic reticulum. , 2010, Organic letters.

[8]  Bernhard Kadenbach,et al.  Intrinsic and extrinsic uncoupling of oxidative phosphorylation. , 2003, Biochimica et biophysica acta.

[9]  H. Vogel,et al.  Labeling of fusion proteins with synthetic fluorophores in live cells. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Jun Feng Zhang,et al.  A lysosome-targeted fluorescent chemodosimeter for monitoring endogenous and exogenous hydrogen sulfide by in vivo imaging. , 2014, Chemical communications.

[11]  A. Ojida,et al.  Development of an AND logic-gate-type fluorescent probe for ratiometric imaging of autolysosome in cell autophagy. , 2015, Chemistry.

[12]  Yi Xiao,et al.  Activatable rotor for quantifying lysosomal viscosity in living cells. , 2013, Journal of the American Chemical Society.

[13]  G. Yin,et al.  A fast-responsive mitochondria-targeted fluorescent probe detecting endogenous hypochlorite in living RAW 264.7 cells and nude mouse. , 2015, Chemical communications.

[14]  Jonathan L. Sessler,et al.  Mitochondria-Immobilized pH-Sensitive Off–On Fluorescent Probe , 2014, Journal of the American Chemical Society.

[15]  Michael S Janes,et al.  Selective fluorescent imaging of superoxide in vivo using ethidium-based probes , 2006, Proceedings of the National Academy of Sciences.

[16]  D. Klionsky,et al.  Autophagosomes, phagosomes, autolysosomes, phagolysosomes, autophagolysosomes… Wait, I’m confused , 2014, Autophagy.

[17]  A. Odermatt,et al.  Green fluorescent protein-based monitoring of endoplasmic reticulum redox poise , 2013, Front. Genet..

[18]  Robin A. J. Smith,et al.  A ratiometric fluorescent probe for assessing mitochondrial phospholipid peroxidation within living cells. , 2012, Free radical biology & medicine.

[19]  Mako Kamiya,et al.  Visualization of phagosomal hydrogen peroxide production by a novel fluorescent probe that is localized via SNAP-tag labeling. , 2014, Analytical chemistry.

[20]  M. Prata,et al.  Mannose-6-phosphate pathway: a review on its role in lysosomal function and dysfunction. , 2012, Molecular genetics and metabolism.

[21]  Chunhui Huang,et al.  Mitochondria-Directed Fluorescent Probe for the Detection of Hydrogen Peroxide near Mitochondrial DNA. , 2015, Analytical chemistry.

[22]  Hwan Myung Kim,et al.  Small-molecule two-photon probes for bioimaging applications. , 2015, Chemical reviews.

[23]  C. S. Lim,et al.  A Two‐Photon Turn‐On Probe for Lipid Rafts with Minimum Internalization , 2011, Chembiochem : a European journal of chemical biology.

[24]  Y. Teramura,et al.  Lectin-tagged fluorescent polymeric nanoparticles for targeting of sialic acid on living cells. , 2014, Biomacromolecules.

[25]  C. Hellberg,et al.  Protein-tyrosine phosphatases and cancer , 2006, Nature Reviews Cancer.

[26]  S. Takeoka,et al.  A ratiometric fluorescent molecular probe for visualization of mitochondrial temperature in living cells. , 2015, Chemical communications.

[27]  Jiangli Fan,et al.  Imaging of lysosomal pH changes with a fluorescent sensor containing a novel lysosome-locating group. , 2012, Chemical communications.

[28]  T. Hurd,et al.  Lipophilic triphenylphosphonium cations as tools in mitochondrial bioenergetics and free radical biology , 2005, Biochemistry (Moscow).

[29]  L. Pike Lipid rafts Published, JLR Papers in Press, February 1, 2003. DOI 10.1194/jlr.R200021-JLR200 , 2003, Journal of Lipid Research.

[30]  Ken Jacobson,et al.  A Role for Lipid Shells in Targeting Proteins to Caveolae, Rafts, and Other Lipid Domains , 2002, Science.

[31]  J. Gustafsson,et al.  Human Mitochondrial Thioredoxin , 2002, The Journal of Biological Chemistry.

[32]  Lin Qiu,et al.  A ratiometric fluorescent probe for rapid detection of hydrogen sulfide in mitochondria. , 2013, Angewandte Chemie.

[33]  U. Brunk,et al.  Lysosomes and oxidative stress in aging and apoptosis. , 2008, Biochimica et biophysica acta.

[34]  Roman S. Erdmann,et al.  Hochaufgelöste Visualisierung des Golgi-Apparats in lebenden Zellen mit einem bioorthogonalen Ceramid† , 2014 .

[35]  C. Kaminski,et al.  Lifetime imaging of a fluorescent protein sensor reveals surprising stability of ER thiol redox , 2013, The Journal of cell biology.

[36]  Robin A. J. Smith,et al.  Mitochondria-targeted small molecule therapeutics and probes. , 2011, Antioxidants & redox signaling.

[37]  Jishan Li,et al.  Selective tracking of lysosomal Cu2+ ions using simultaneous target- and location-activated fluorescent nanoprobes. , 2015, Analytical chemistry.

[38]  Alexander A. Kantardjiev,et al.  PHEPS: web-based pH-dependent Protein Electrostatics Server , 2006, Nucleic Acids Res..

[39]  D. Klein,et al.  Association of copper to metallothionein in hepatic lysosomes of Long–Evans cinnamon (LEC) rats during the development of hepatitis , 1998, European journal of clinical investigation.

[40]  A. Palmer,et al.  Visualizing metal ions in cells: an overview of analytical techniques, approaches, and probes. , 2012, Biochimica et biophysica acta.

[41]  K. Johnsson,et al.  Indo-1 derivatives for local calcium sensing. , 2009, ACS chemical biology.

[42]  P. Yeagle,et al.  The membranes of cells , 1987 .

[43]  Jing Qiao,et al.  Multifunctional self-assembled polymeric nanoprobes for FRET-based ratiometric detection of mitochondrial H2O2 in living cells. , 2015, Chemical communications.

[44]  Edward T Chouchani,et al.  Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS , 2014, Nature.

[45]  P. Dutta,et al.  Rapid Synthesis Method of Faujasitic Zeolite Frameworks Probed with Eu(III) Fluorescence Spectroscopy , 2015 .

[46]  A. Ojida,et al.  Organelle-localizable fluorescent chemosensors for site-specific multicolor imaging of nucleoside polyphosphate dynamics in living cells. , 2012, Journal of the American Chemical Society.

[47]  R. Tsien,et al.  Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores. , 1989, The Journal of biological chemistry.

[48]  J. Ellenberg,et al.  Formation of the nuclear envelope permeability barrier studied by sequential photoswitching and flux analysis. , 2009, Biophysical journal.

[49]  D. Kell,et al.  Genetics and iron in the systems biology of Parkinson’s disease and some related disorders , 2013, Neurochemistry International.

[50]  S. Yoshikawa,et al.  Proton pumping mechanism of bovine heart cytochrome c oxidase. , 2006, Biochimica et biophysica acta.

[51]  Shishido,et al.  MKT-077, a novel rhodacyanine dye in clinical trials, exhibits anticarcinoma activity in preclinical studies based on selective mitochondrial accumulation. , 1996, Cancer research.

[52]  U. Schaible,et al.  Targeting the lysosome: fluorescent iron(III) chelators to selectively monitor endosomal/lysosomal labile iron pools. , 2008, Journal of medicinal chemistry.

[53]  Ke Wen,et al.  Phospholipid-bound molecular rotors: synthesis and characterization. , 2002, Bioorganic & medicinal chemistry.

[54]  Ru Sun,et al.  N-Pyridineium-2-yl Darrow Red analogue: unique near-infrared lysosome-biomarker for the detection of cancer cells. , 2015, Analytical chemistry.

[55]  S. Kelley,et al.  Mitochondria-penetrating peptides. , 2008, Chemistry & biology.

[56]  A. Crofts,et al.  The cytochrome bc1 complex: function in the context of structure. , 2004, Annual review of physiology.

[57]  Jiahuai Han,et al.  Rhodamine-propargylic esters for detection of mitochondrial hydrogen sulfide in living cells. , 2013, Bioorganic & medicinal chemistry letters.

[58]  Mathew Tantama,et al.  S 1 Imaging Intracellular pH in Live Cells with a Genetically-Encoded Red Fluorescent Protein Sensor , 2011 .

[59]  A. Baracca,et al.  Rhodamine 123 as a probe of mitochondrial membrane potential: evaluation of proton flux through F(0) during ATP synthesis. , 2003, Biochimica et biophysica acta.

[60]  Junle Qu,et al.  Dual mode monitoring probe for mitochondrial viscosity in single cell , 2014 .

[61]  T. von Zglinicki,et al.  Relocalized redox-active lysosomal iron is an important mediator of oxidative-stress-induced DNA damage. , 2004, The Biochemical journal.

[62]  S. Fraser,et al.  Mitochondrially targeted redox probe reveals the variations in oxidative capacity of the haematopoietic cells. , 2015, Organic & biomolecular chemistry.

[63]  Thomas V. O'Halloran,et al.  Transition Metal Speciation in the Cell: Insights from the Chemistry of Metal Ion Receptors , 2003, Science.

[64]  Mark P Mattson,et al.  Calcium signaling in the ER: its role in neuronal plasticity and neurodegenerative disorders , 2000, Trends in Neurosciences.

[65]  N. Tonks,et al.  Protein tyrosine phosphatases: from genes, to function, to disease , 2006, Nature Reviews Molecular Cell Biology.

[66]  B. Rost,et al.  Finding nuclear localization signals , 2000, EMBO reports.

[67]  K. Svoboda,et al.  A genetically encoded fluorescent sensor of ERK activity , 2008, Proceedings of the National Academy of Sciences.

[68]  N. Jana,et al.  Design and Synthesis of Triphenylphosphonium Functionalized Nanoparticle Probe for Mitochondria Targeting and Imaging , 2015 .

[69]  Mark A Haidekker,et al.  Characterization of changes in the viscosity of lipid membranes with the molecular rotor FCVJ. , 2008, Biochimica et biophysica acta.

[70]  Jun Feng Zhang,et al.  Recent progress in fluorescent and colorimetric chemosensors for detection of precious metal ions (silver, gold and platinum ions). , 2011, Chemical Society reviews.

[71]  G. Link,et al.  Action of chelators in iron-loaded cardiac cells: Accessibility to intracellular labile iron and functional consequences. , 2006, Blood.

[72]  Guoying Zhang,et al.  Spatiotemporal monitoring endocytic and cytosolic pH gradients with endosomal escaping pH-responsive micellar nanocarriers. , 2014, Biomacromolecules.

[73]  G. Rotilio,et al.  Mitochondrial Dysfunction in Neurodegenerative Diseases Associated with Copper Imbalance , 2004, Neurochemical Research.

[74]  J. Eaton,et al.  Radiation-induced cell death: importance of lysosomal destabilization. , 2005, The Biochemical journal.

[75]  A. Colell,et al.  Mitochondrial glutathione, a key survival antioxidant. , 2009, Antioxidants & redox signaling.

[76]  C. Cairo,et al.  Fluorescent small-molecule probes of biochemistry at the plasma membrane. , 2010, Current opinion in chemical biology.

[77]  D. Klionsky,et al.  Regulation mechanisms and signaling pathways of autophagy. , 2009, Annual review of genetics.

[78]  Yumin Zhang,et al.  Visible light excitable Zn2+ fluorescent sensor derived from an intramolecular charge transfer fluorophore and its in vitro and in vivo application. , 2009, Journal of the American Chemical Society.

[79]  John R. Allen,et al.  A fluorescent indicator for imaging lysosomal zinc(II) with Förster resonance energy transfer (FRET)-enhanced photostability and a narrow band of emission. , 2015, Chemistry.

[80]  K. Cheah,et al.  Two-photon fluorescence probes for imaging of mitochondria and lysosomes. , 2013, Chemical communications.

[81]  Satoshi Arai,et al.  A Molecular Fluorescent Probe for Targeted Visualization of Temperature at the Endoplasmic Reticulum , 2014, Scientific Reports.

[82]  Yan-hong Liu,et al.  A ratiometric fluorescent probe for in situ quantification of basal mitochondrial hypochlorite in cancer cells. , 2015, Chemical communications.

[83]  M. Taki,et al.  Development of a cholesterol-conjugated fluorescent sensor for site-specific detection of zinc ion at the plasma membrane. , 2011, Organic letters.

[84]  P. W. Janes,et al.  Aggregation of Lipid Rafts Accompanies Signaling via the T Cell Antigen Receptor , 1999, The Journal of cell biology.

[85]  G. Cosa,et al.  Fluorogenic α-tocopherol analogue for monitoring the antioxidant status within the inner mitochondrial membrane of live cells. , 2013, Journal of the American Chemical Society.

[86]  Christopher J. Chang,et al.  A targetable fluorescent sensor reveals that copper-deficient SCO1 and SCO2 patient cells prioritize mitochondrial copper homeostasis. , 2011, Journal of the American Chemical Society.

[87]  Lingxin Chen,et al.  A near-infrared ratiometric fluorescent probe for cysteine detection over glutathione indicating mitochondrial oxidative stress in vivo. , 2015, Biosensors & bioelectronics.

[88]  Satoshi Arai,et al.  Mitochondria-targeted fluorescent thermometer monitors intracellular temperature gradient. , 2015, Chemical communications.

[89]  A Miyawaki,et al.  Measurement of cytosolic, mitochondrial, and Golgi pH in single living cells with green fluorescent proteins. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[90]  Young‐Tae Chang,et al.  Development of targetable two-photon fluorescent probes to image hypochlorous Acid in mitochondria and lysosome in live cell and inflamed mouse model. , 2015, Journal of the American Chemical Society.

[91]  Richard W. Horobin,et al.  Fluorescent cationic probes for nuclei of living cells: why are they selective? A quantitative structure–activity relations analysis , 2006, Histochemistry and Cell Biology.

[92]  M. Beal,et al.  Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases , 2006, Nature.

[93]  W. Junger,et al.  Immune cell regulation by autocrine purinergic signalling , 2011, Nature Reviews Immunology.

[94]  N. Mizushima,et al.  Autophagosome formation in mammalian cells. , 2002, Cell structure and function.

[95]  Chulhong Kim,et al.  Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents. , 2011, Nature materials.

[96]  Henry Jay Forman,et al.  Redox signaling , 2004, Molecular and Cellular Biochemistry.

[97]  Kemin Wang,et al.  Inorganic fluorescent nanoprobes for cellular and subcellular imaging , 2014 .

[98]  Cahir J. O'Kane,et al.  Complex Inhibitory Effects of Nitric Oxide on Autophagy , 2011, Molecular cell.

[99]  M. Taki,et al.  Rosamine-based fluorescent sensor with femtomolar affinity for the reversible detection of a mercury ion. , 2012, Inorganic chemistry.

[100]  B. Tang,et al.  A selective near-infrared fluorescent probe for singlet oxygen in living cells. , 2011, Chemical communications.

[101]  Fengling Song,et al.  A novel fluorescent sensor for detection of highly reactive oxygen species, and for imaging such endogenous hROS in the mitochondria of living cells. , 2013, The Analyst.

[102]  Jong Seung Kim,et al.  BODIPY-Coumarin Conjugate as an Endoplasmic Reticulum Membrane Fluidity Sensor and Its Application to ER Stress Models. , 2015, Bioconjugate chemistry.

[103]  P. Robbins,et al.  Transporters of nucleotide sugars, ATP, and nucleotide sulfate in the endoplasmic reticulum and Golgi apparatus. , 1998, Annual review of biochemistry.

[104]  R W Horobin,et al.  Why fluorescent probes for endoplasmic reticulum are selective: an experimental and QSAR-modelling study , 2003, Biotechnic & histochemistry : official publication of the Biological Stain Commission.

[105]  Ji Hee Han,et al.  In vivo imaging of near-membrane calcium ions with two-photon probes. , 2011, Chemistry, an Asian journal.

[106]  Y. Liu,et al.  A near-infrared fluorescent probe for detecting copper(II) with high selectivity and sensitivity and its biological imaging applications. , 2011, Chemical communications.

[107]  D. Hammer,et al.  In vivo fluorescence imaging: a personal perspective. , 2009, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[108]  Takayoshi Suzuki,et al.  Novel mitochondria-localizing TEMPO derivative for measurement of cellular oxidative stress in mitochondria. , 2007, Bioorganic & medicinal chemistry letters.

[109]  Ji Hee Han,et al.  A mitochondrial-targeted two-photon probe for zinc ion. , 2011, Journal of the American Chemical Society.

[110]  R. Parton,et al.  Not just fat: the structure and function of the lipid droplet. , 2011, Cold Spring Harbor perspectives in biology.

[111]  Kai Johnsson,et al.  Localizable and highly sensitive calcium indicator based on a BODIPY fluorophore. , 2010, Analytical chemistry.

[112]  J. Koh,et al.  Roles of zinc and metallothionein-3 in oxidative stress-induced lysosomal dysfunction, cell death, and autophagy in neurons and astrocytes , 2010, Molecular Brain.

[113]  M. Rissel,et al.  The B[a]P-increased intercellular communication via translocation of connexin-43 into gap junctions reduces apoptosis. , 2010, Toxicology and applied pharmacology.

[114]  Jin Zhao,et al.  A colorimetric and ratiometric fluorescent probe for ClO- targeting in mitochondria and its application in vivo. , 2015, Journal of materials chemistry. B.

[115]  C. S. Lim,et al.  A two-photon probe for near-membrane zinc ions , 2014 .

[116]  Jianhua Zhang,et al.  Reduction of mutant huntingtin accumulation and toxicity by lysosomal cathepsins D and B in neurons , 2011, Molecular Neurodegeneration.

[117]  J. Queiroz,et al.  Targeting of Mitochondria-Endoplasmic Reticulum by Fluorescent Macrocyclic Compounds , 2011, PloS one.

[118]  C. Gay,et al.  Characterization of Calcium Translocation across the Plasma Membrane of Primary Osteoblasts Using a Lipophilic Calcium-sensitive Fluorescent Dye, Calcium Green C18(*) , 1995, The Journal of Biological Chemistry.

[119]  Guichao Kuang,et al.  BODIPY-based fluorescent thermometer as a lysosome-targetable probe: how the oligo(ethylene glycols) compete photoinduced electron transfer. , 2015, Chemistry.

[120]  Luís M. S. Loura,et al.  Recent Developments in Molecular Dynamics Simulations of Fluorescent Membrane Probes , 2011, Molecules.

[121]  D. Zakim,et al.  Are membrane enzymes regulated by the viscosity of the membrane environment? , 1992, Biochemistry.

[122]  U. Brunk,et al.  Lysosomes in iron metabolism, ageing and apoptosis , 2008, Histochemistry and Cell Biology.

[123]  T. Gunnlaugsson,et al.  Luminescent ruthenium(II) polypyridyl functionalized gold nanoparticles; their DNA binding abilities and application as cellular imaging agents. , 2011, Journal of the American Chemical Society.

[124]  P. Rich The molecular machinery of Keilin's respiratory chain. , 2003, Biochemical Society transactions.

[125]  N. LaRusso,et al.  Biliary copper excretion by hepatocyte lysosomes in the rat. Major excretory pathway in experimental copper overload. , 1989, The Journal of clinical investigation.

[126]  P. Perlman,et al.  Targeting of green fluorescent protein to mitochondria. , 2001, Methods in cell biology.

[127]  M. Mattson,et al.  Superoxide Flashes in Single Mitochondria , 2008, Cell.

[128]  Zhen Cheng,et al.  Design, synthesis and biological evaluation of mitochondria targeting theranostic agents. , 2014, Chemical communications.

[129]  M. Distefano,et al.  Bioanalysis of eukaryotic organelles. , 2013, Chemical reviews.

[130]  C. Tung,et al.  A non-toxic fluorogenic dye for mitochondria labeling. , 2013, Biochimica et biophysica acta.

[131]  M. Tan,et al.  A mitochondria-targeted fluorescent probe based on TPP-conjugated carbon dots for both one- and two-photon fluorescence cell imaging , 2014 .

[132]  Liyan Cao,et al.  A ruthenium(II) complex-based lysosome-targetable multisignal chemosensor for in vivo detection of hypochlorous acid. , 2015, Biomaterials.

[133]  Chulhun Kang,et al.  A Nile Red/BODIPY-based bimodal probe sensitive to changes in the micropolarity and microviscosity of the endoplasmic reticulum. , 2014, Chemical communications.

[134]  Y. Urano,et al.  Design and synthesis of fluorescent probes for selective detection of highly reactive oxygen species in mitochondria of living cells. , 2007, Journal of the American Chemical Society.

[135]  Jonathan L Sessler,et al.  Small molecule-based ratiometric fluorescence probes for cations, anions, and biomolecules. , 2015, Chemical Society reviews.

[136]  Gillian M. Griffiths,et al.  Linking Albinism and Immunity: The Secrets of Secretory Lysosomes , 2004, Science.

[137]  R. Pal,et al.  Live cell imaging of lysosomal pH changes with pH responsive ratiometric lanthanide probes. , 2012, Chemical communications.

[138]  Jianjun Du,et al.  Lighting up fluoride ions in cellular mitochondria using a highly selective and sensitive fluorescent probe. , 2014, Chemical communications.

[139]  S. Singer,et al.  The Fluid Mosaic Model of the Structure of Cell Membranes , 1972, Science.

[140]  Stefan W. Hell,et al.  SiR–Hoechst is a far-red DNA stain for live-cell nanoscopy , 2015, Nature Communications.

[141]  C. S. Lim,et al.  A highly sensitive two-photon fluorescent probe for mitochondrial zinc ions in living tissue. , 2012, Chemical communications.

[142]  Yoichi Shimizu,et al.  Investigation of cyanine dyes for in vivo optical imaging of altered mitochondrial membrane potential in tumors , 2014, Cancer medicine.

[143]  Chen-Ho Tung,et al.  Design strategies of fluorescent probes for selective detection among biothiols. , 2015, Chemical Society reviews.

[144]  J A Frangos,et al.  New fluorescent probes for the measurement of cell membrane viscosity. , 2001, Chemistry & biology.

[145]  B. Böttcher,et al.  The gross structure of the respiratory complex I: a Lego System. , 2004, Biochimica et biophysica acta.

[146]  Xiaobing Zhang,et al.  An efficient ratiometric fluorescent probe for tracking dynamic changes in lysosomal pH. , 2015, The Analyst.

[147]  S. Fowler,et al.  Nile red: a selective fluorescent stain for intracellular lipid droplets , 1985, The Journal of cell biology.

[148]  Christopher J. Chang,et al.  A nuclear-localized fluorescent hydrogen peroxide probe for monitoring sirtuin-mediated oxidative stress responses in vivo. , 2011, Chemistry & biology.

[149]  Jiahuai Han,et al.  Covalent labeling of mitochondria with a photostable fluorescent thiol-reactive rhodamine-based probe , 2012 .

[150]  Jun‐Long Zhang,et al.  Combining myeloperoxidase (MPO) with fluorogenic ZnSalen to detect lysosomal hydrogen peroxide in live cells , 2013 .

[151]  Debabrata Sen,et al.  A ratiometric two-photon fluorescent probe reveals reduction in mitochondrial H2S production in Parkinson's disease gene knockout astrocytes. , 2013, Journal of the American Chemical Society.

[152]  B. Liu,et al.  A small-molecule FRET reporter for the real-time visualization of cell-surface proteolytic enzyme functions. , 2014, Angewandte Chemie.

[153]  J. Loscalzo,et al.  Genetically encoded fluorescent sensors for intracellular NADH detection. , 2011, Cell metabolism.

[154]  A. Parekh,et al.  Ca2+ microdomains near plasma membrane Ca2+ channels: impact on cell function , 2008, The Journal of physiology.

[155]  T. Wei,et al.  Plasma membrane calcium ATPase 4b inhibits nitric oxide generation through calcium-induced dynamic interaction with neuronal nitric oxide synthase , 2013, Protein & Cell.

[156]  M L Walsh,et al.  Localization of mitochondria in living cells with rhodamine 123. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[157]  S. Munro Lipid Rafts Elusive or Illusive? , 2003, Cell.

[158]  Lawrence M. Lifshitz,et al.  Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. , 1998, Science.

[159]  B. Cho,et al.  A Two‐Photon Fluorescent Probe for Lipid Raft Imaging: C‐Laurdan , 2007, Chembiochem : a European journal of chemical biology.

[160]  Jing Zhang,et al.  Rhodamine-based fluorescent probe for direct bio-imaging of lysosomal pH changes. , 2014, Talanta.

[161]  Satoru Kobayashi,et al.  Choose Delicately and Reuse Adequately: The Newly Revealed Process of Autophagy. , 2015, Biological & pharmaceutical bulletin.

[162]  Yingying Huo,et al.  A mitochondria-targetable fluorescent probe for peroxynitrite: fast response and high selectivity. , 2015, Chemical communications.

[163]  Ben Zhong Tang,et al.  A fluorescent light-up probe with "AIE + ESIPT" characteristics for specific detection of lysosomal esterase. , 2014, Journal of materials chemistry. B.

[164]  A S Verkman,et al.  Green fluorescent protein as a noninvasive intracellular pH indicator. , 1998, Biophysical journal.

[165]  Lin Yuan,et al.  FRET-based mitochondria-targetable dual-excitation ratiometric fluorescent probe for monitoring hydrogen sulfide in living cells. , 2014, Chemistry, an Asian journal.

[166]  Y. Kalaidzidis,et al.  Rab Conversion as a Mechanism of Progression from Early to Late Endosomes , 2005, Cell.

[167]  B. Tang,et al.  Advances in functional fluorescent and luminescent probes for imaging intracellular small-molecule reactive species , 2012 .

[168]  B. Lai,et al.  Imaging of the intracellular topography of copper with a fluorescent sensor and by synchrotron x-ray fluorescence microscopy. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[169]  Qinglong Qiao,et al.  A turn-on fluorescent probe for imaging lysosomal hydrogen sulfide in living cells , 2014 .

[170]  L. Yin,et al.  Lysosomal and mitochondrial pathways in H2O2‐induced apoptosis of alveolar type II cells , 2005, Journal of cellular biochemistry.

[171]  I. McInnes,et al.  Cellular imaging in rheumatic diseases , 2015, Nature Reviews Rheumatology.

[172]  M. Teulade‐Fichou,et al.  N-phenyl-carbazole-based two-photon fluorescent probes: strong sequence dependence of the duplex vs quadruplex selectivity. , 2011, Biochimie.

[173]  I. Piantanida,et al.  A molecular peptide beacon for the ratiometric sensing of nucleic acids. , 2012, Journal of the American Chemical Society.

[174]  Haibo Yu,et al.  Targetable fluorescent probe for monitoring exogenous and endogenous NO in mitochondria of living cells. , 2013, Analytical chemistry.

[175]  Fang Zeng,et al.  A targeted and FRET-based ratiometric fluorescent nanoprobe for imaging mitochondrial hydrogen peroxide in living cells. , 2014, Small.

[176]  Geoffrey Burnstock,et al.  Purinergic Signalling: ATP Release , 2001, Neurochemical Research.

[177]  W. Gahl,et al.  Disorders of lysosome-related organelle biogenesis: clinical and molecular genetics. , 2008, Annual review of genomics and human genetics.

[178]  V. Villiotou,et al.  Modulation of particulate nitric oxide synthase activity and peroxynitrite synthesis in cholesterol enriched endothelial cell membranes. , 1995, Biochemical pharmacology.

[179]  C. Winterbourn,et al.  Reconciling the chemistry and biology of reactive oxygen species. , 2008, Nature chemical biology.

[180]  Guanying Li,et al.  Phosphorescent iridium(iii) complexes as multicolour probes for imaging of hypochlorite ions in mitochondria. , 2014, Journal of materials chemistry. B.

[181]  Ji Hee Han,et al.  Dual-color imaging of sodium/calcium ion activities with two-photon fluorescent probes. , 2010, Angewandte Chemie.

[182]  Jong Seung Kim,et al.  Organelle-selective fluorescent Cu2+ ion probes: revealing the endoplasmic reticulum as a reservoir for Cu-overloading. , 2014, Chemical communications.

[183]  Fengling Song,et al.  Ratiometric detection of viscosity using a two-photon fluorescent sensor. , 2013, Chemistry.

[184]  A. Slusarenko,et al.  The biology of reactive sulfur species (RSS). , 2012, Plant physiology and biochemistry : PPB.

[185]  D. Churchill,et al.  Selenium- and tellurium-containing fluorescent molecular probes for the detection of biologically important analytes. , 2014, Accounts of chemical research.

[186]  X. Duan,et al.  Comparison of Staining Selectivity for Subcellular Structures by Carbazole‐Based Cyanine Probes in Nonlinear Optical Microscopy , 2011, Chembiochem : a European journal of chemical biology.

[187]  S. Kelley,et al.  Targeting Mitochondria with Organelle‐Specific Compounds: Strategies and Applications , 2009, Chembiochem : a European journal of chemical biology.

[188]  Peng Li,et al.  Redox-Responsive Fluorescent Probes with Different Design Strategies. , 2015, Accounts of chemical research.

[189]  Robert E. Campbell,et al.  pHuji, a pH-sensitive red fluorescent protein for imaging of exo- and endocytosis , 2014, The Journal of cell biology.

[190]  E. Gratton,et al.  Two-photon fluorescence microscopy of laurdan generalized polarization domains in model and natural membranes. , 1997, Biophysical journal.

[191]  B. Tang,et al.  A near-infrared fluorescent probe for monitoring ozone and imaging in living cells. , 2012, Chemical communications.

[192]  S. Lippard,et al.  Visualization of peroxynitrite-induced changes of labile Zn2+ in the endoplasmic reticulum with benzoresorufin-based fluorescent probes. , 2013, Journal of the American Chemical Society.

[193]  Robin A. J. Smith,et al.  Targeting lipoic acid to mitochondria: synthesis and characterization of a triphenylphosphonium-conjugated alpha-lipoyl derivative. , 2007, Free radical biology & medicine.

[194]  M. Garnett,et al.  Targeted drug conjugates: principles and progress. , 2001, Advanced drug delivery reviews.

[195]  Wei Feng,et al.  Luminescent chemodosimeters for bioimaging. , 2013, Chemical reviews.

[196]  T. James,et al.  Glucose Sensing in Supramolecular Chemistry. , 2015, Chemical reviews.

[197]  Suming Chen,et al.  Lysosomal pH rise during heat shock monitored by a lysosome-targeting near-infrared ratiometric fluorescent probe. , 2014, Angewandte Chemie.

[198]  Liang Zhao,et al.  A highly selective and sensitive ON-OFF-ON fluorescence chemosensor for cysteine detection in endoplasmic reticulum. , 2015, Biosensors & bioelectronics.

[199]  G. Burnstock Pathophysiology and Therapeutic Potential of Purinergic Signaling , 2006, Pharmacological Reviews.

[200]  Juyoung Yoon,et al.  Visualization of Endogenous and Exogenous Hydrogen Peroxide Using A Lysosome-Targetable Fluorescent Probe , 2015, Scientific Reports.

[201]  M. Elkalaf,et al.  Lipophilic Triphenylphosphonium Cations Inhibit Mitochondrial Electron Transport Chain and Induce Mitochondrial Proton Leak , 2015, PloS one.

[202]  Juyoung Yoon,et al.  Recent progress in fluorescent and colorimetric chemosensors for detection of amino acids. , 2012, Chemical Society reviews.

[203]  C. Isidoro,et al.  Involvement of autophagy in ovarian cancer: a working hypothesis , 2012, Journal of Ovarian Research.

[204]  S. Lippard,et al.  Peptide Targeting of Fluorescein-Based Sensors to Discrete Intracellular Locales. , 2014, Chemical science.

[205]  J. Tschopp,et al.  Thioredoxin-interacting protein links oxidative stress to inflammasome activation , 2010, Nature Immunology.

[206]  T. Steck THE ORGANIZATION OF PROTEINS IN THE HUMAN RED BLOOD CELL MEMBRANE , 1974, The Journal of cell biology.

[207]  K. Kashfi,et al.  Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras. , 2013, Biochemical pharmacology.

[208]  Jong Seung Kim,et al.  Mitochondrial thioredoxin-responding off-on fluorescent probe. , 2012, Journal of the American Chemical Society.

[209]  T. Schlüter,et al.  Protection of mitochondrial integrity from oxidative stress by the triaminopyridine derivative flupirtine , 2000, FEBS letters.

[210]  M. Kuimova,et al.  Membrane-Bound Molecular Rotors Measure Viscosity in Live Cells via Fluorescence Lifetime Imaging , 2009 .

[211]  Mark A Haidekker,et al.  Molecular rotors--fluorescent biosensors for viscosity and flow. , 2007, Organic & biomolecular chemistry.

[212]  C. Nguyen,et al.  BENA435, a new cell-permeant photoactivated green fluorescent DNA probe , 2006, Nucleic acids research.

[213]  D. Lodygin,et al.  A combination of fluorescent NFAT and H2B sensors uncovers dynamics of T cell activation in real time during CNS autoimmunity , 2013, Nature Medicine.

[214]  I. Mellman Endocytosis and molecular sorting. , 1996, Annual review of cell and developmental biology.

[215]  I. Johnson,et al.  The molecular probes handbook : a guide to fluorescent probes and labeling technologies , 2010 .

[216]  C. L. Teoh,et al.  A mitochondria-targeted ratiometric fluorescent probe to monitor endogenously generated sulfur dioxide derivatives in living cells. , 2015, Biomaterials.

[217]  Xiaoqing Xiong,et al.  Ratiometric fluorescence imaging of cellular polarity: decrease in mitochondrial polarity in cancer cells. , 2015, Angewandte Chemie.

[218]  J. Mindell Lysosomal acidification mechanisms. , 2012, Annual review of physiology.

[219]  A. Tanimura,et al.  Monitoring of Ca2+ release from intracellular stores in permeabilized rat parotid acinar cells using the fluorescent indicators Mag-fura-2 and calcium green C18. , 1997, Biochemical and biophysical research communications.

[220]  Takayoshi Suzuki,et al.  Development of a DNA-binding TEMPO derivative for evaluation of nuclear oxidative stress and its application in living cells. , 2010, Free radical biology & medicine.

[221]  J. Mandl,et al.  Endoplasmic Reticulum: Nutrient Sensor in Physiology and Pathology , 2022 .

[222]  U. Schaible,et al.  Monitoring intracellular labile iron pools: A novel fluorescent iron(III) sensor as a potential non-invasive diagnosis tool. , 2009, Journal of pharmaceutical sciences.

[223]  C. Chinopoulos,et al.  Mitochondria as ATP consumers in cellular pathology. , 2010, Biochimica et biophysica acta.

[224]  J. Paul Luzio,et al.  Lysosomes: fusion and function , 2007, Nature Reviews Molecular Cell Biology.

[225]  Bin Liu,et al.  Mitochondria-targeted cancer therapy using a light-up probe with aggregation-induced-emission characteristics. , 2014, Angewandte Chemie.

[226]  Koen Clays,et al.  Molecular engineering of chromophores for combined second-harmonic and two-photon fluorescence in cellular imaging , 2012 .

[227]  Atsushi Miyawaki,et al.  A sensitive and quantitative technique for detecting autophagic events based on lysosomal delivery. , 2011, Chemistry & biology.

[228]  Ping Li,et al.  A near-infrared-emitting fluorescent probe for monitoring mitochondrial pH. , 2014, Chemical communications.

[229]  Guoping Li,et al.  Rational design of a ratiometric and targetable fluorescent probe for imaging lysosomal zinc ions. , 2012, Inorganic chemistry.

[230]  C. S. Lim,et al.  A two-photon fluorescent probe for near-membrane calcium ions in live cells and tissues. , 2009, Chemical communications.

[231]  S. Kelley,et al.  Mitochondria‐Penetrating Peptides: Sequence Effects and Model Cargo Transport , 2009, Chembiochem : a European journal of chemical biology.

[232]  M. Guo,et al.  A Turn‐on Fluorescent Sensor for Imaging Labile Fe3+ in Live Neuronal Cells at Subcellular Resolution , 2012, Chembiochem : a European journal of chemical biology.

[233]  Andreas J Meyer,et al.  Real-time imaging of the intracellular glutathione redox potential , 2008, Nature Methods.

[234]  Mark A Haidekker,et al.  Environment-sensitive behavior of fluorescent molecular rotors , 2010, Journal of biological engineering.

[235]  K. Ahn,et al.  A two-photon fluorescent probe for lysosomal zinc ions. , 2016, Chemical communications.

[236]  H. McMahon,et al.  Mechanisms of endocytosis. , 2009, Annual review of biochemistry.

[237]  H. Vogel,et al.  A general method for the covalent labeling of fusion proteins with small molecules in vivo , 2003, Nature Biotechnology.

[238]  P. Choyke,et al.  New strategies for fluorescent probe design in medical diagnostic imaging. , 2010, Chemical reviews.

[239]  Yi Xiao,et al.  Monitoring lipid peroxidation within foam cells by lysosome-targetable and ratiometric probe. , 2015, Analytical chemistry.

[240]  A. Tiwari,et al.  pH-activatable near-infrared fluorescent probes for detection of lysosomal pH inside living cells. , 2014, Journal of materials chemistry. B.

[241]  A. Tiwari,et al.  Near-infrared fluorescent probes based on piperazine-functionalized BODIPY dyes for sensitive detection of lysosomal pH. , 2015, Journal of materials chemistry. B.

[242]  Young Ho Suh,et al.  Red emissive two-photon probe for real-time imaging of mitochondria trafficking. , 2014, Analytical chemistry.

[243]  C. Legrand,et al.  Mitochondria-targeted cpYFP: pH or superoxide sensor? , 2012, The Journal of general physiology.

[244]  Fengling Song,et al.  A BODIPY-based fluorescent dye for mitochondria in living cells, with low cytotoxicity and high photostability. , 2013, Organic & biomolecular chemistry.

[245]  Peng Li,et al.  Development of a selenide-based fluorescent probe for imaging hypochlorous acid in lysosomes , 2015 .

[246]  Ismael López-Duarte,et al.  A molecular rotor for measuring viscosity in plasma membranes of live cells. , 2014, Chemical communications.

[247]  Yuncong Chen,et al.  An excitation ratiometric Zn2+ sensor with mitochondria-targetability for monitoring of mitochondrial Zn2+ release upon different stimulations. , 2012, Chemical communications.

[248]  A. Palmer,et al.  Measuring steady-state and dynamic endoplasmic reticulum and Golgi Zn2+ with genetically encoded sensors , 2011, Proceedings of the National Academy of Sciences.

[249]  Xinghui Gao,et al.  HOCl can appear in the mitochondria of macrophages during bacterial infection as revealed by a sensitive mitochondrial-targeting fluorescent probe† †Electronic supplementary information (ESI) available: Experimental section and supporting figures. See DOI: 10.1039/c5sc01562f Click here for additiona , 2015, Chemical science.

[250]  Robin A. J. Smith,et al.  Targeting antioxidants to mitochondria by conjugation to lipophilic cations. , 2007, Annual review of pharmacology and toxicology.

[251]  G. Mancini,et al.  Characterization of a heavy metal ion transporter in the lysosomal membrane , 1998, FEBS letters.

[252]  Lei Guo,et al.  Indole-based cyanine as a nuclear RNA-selective two-photon fluorescent probe for live cell imaging. , 2015, ACS chemical biology.

[253]  Jiangli Fan,et al.  Fluorene-derived two-photon fluorescent probes for specific and simultaneous bioimaging of endoplasmic reticulum and lysosomes: group-effect and localization. , 2013, Journal of materials chemistry. B.

[254]  Limin Yang,et al.  Real-time imaging of mitochondrial hydrogen peroxide and pH fluctuations in living cells using a fluorescent nanosensor. , 2015, Analytical chemistry.

[255]  Michael Reth,et al.  Hydrogen peroxide as second messenger in lymphocyte activation , 2002, Nature Immunology.

[256]  Zhaochao Xu,et al.  Fluorescence imaging of metal ions implicated in diseases. , 2015, Chemical Society reviews.

[257]  C. S. Lim,et al.  A mitochondria-localized two-photon fluorescent probe for ratiometric imaging of hydrogen peroxide in live tissue. , 2012, Chemical communications.

[258]  A. Bhattacharjee,et al.  New fluoranthene FLUN-550 as a fluorescent probe for selective staining and quantification of intracellular lipid droplets. , 2014, Organic letters.

[259]  Roger Y. Tsien,et al.  A New Cell-Permeable Fluorescent Probe for Zn2+ , 2000 .

[260]  Kun Li,et al.  Mitochondria-targeted ratiometric fluorescent probe for real time monitoring of pH in living cells. , 2015, Biomaterials.

[261]  C. Tung,et al.  Design and synthesis of a mitochondria-targeting carrier for small molecule drugs. , 2014, Organic & biomolecular chemistry.

[262]  K. Higaki,et al.  Decreased membrane fluidity and unsaturated fatty acids in Niemann-Pick disease type C fibroblasts. , 1998, Biochimica et biophysica acta.

[263]  Robin A. J. Smith,et al.  Mitochondria-targeted antioxidants as therapies. , 2011, Discovery medicine.

[264]  S. Rhee,et al.  A fluorescence turn-on H2O2 probe exhibits lysosome-localized fluorescence signals. , 2012, Chemical communications.

[265]  P. Weitzman,et al.  Krebs' citric acid cycle : half a century and still turning , 1987 .

[266]  F. Fay,et al.  Detection of changes in near-membrane Ca2+ concentration using a novel membrane-associated Ca2+ indicator. , 1994, The Journal of biological chemistry.

[267]  B. Tang,et al.  Water-soluble tetraphenylethene derivatives as fluorescent "light-up" probes for nucleic acid detection and their applications in cell imaging. , 2013, Chemistry, an Asian journal.

[268]  Ben Zhong Tang,et al.  A photostable AIE luminogen for specific mitochondrial imaging and tracking. , 2013, Journal of the American Chemical Society.

[269]  M. Toledano,et al.  ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis , 2007, Nature Reviews Molecular Cell Biology.

[270]  D. Meldrum,et al.  A highly selective mitochondria-targeting fluorescent K(+) sensor. , 2015, Angewandte Chemie.

[271]  K. Gee,et al.  A new mitochondrial fluorescent zinc sensor. , 2003, Cell calcium.

[272]  Soo-Yeon Lim,et al.  Tunable heptamethine-azo dye conjugate as an NIR fluorescent probe for the selective detection of mitochondrial glutathione over cysteine and homocysteine. , 2014, Journal of the American Chemical Society.

[273]  W. Tan,et al.  Design of a simultaneous target and location-activatable fluorescent probe for visualizing hydrogen sulfide in lysosomes. , 2014, Analytical chemistry.

[274]  Jiangli Fan,et al.  A highly specific BODIPY-based probe localized in mitochondria for HClO imaging. , 2013, The Analyst.

[275]  T. Chiles,et al.  Deconvolution of the cellular oxidative stress response with organelle-specific Peptide conjugates. , 2007, Chemistry & biology.

[276]  Jia Ge,et al.  Fluorescence activation imaging of cytochrome c released from mitochondria using aptameric nanosensor. , 2015, Journal of the American Chemical Society.

[277]  B. Tang,et al.  A near-infrared reversible fluorescent probe for real-time imaging of redox status changes in vivo , 2013 .

[278]  F. Petrat,et al.  Selective determination of mitochondrial chelatable iron in viable cells with a new fluorescent sensor. , 2002, The Biochemical journal.

[279]  B. Dickinson,et al.  A targetable fluorescent probe for imaging hydrogen peroxide in the mitochondria of living cells. , 2008, Journal of the American Chemical Society.

[280]  Jason J. Davis,et al.  A turn-on fluorescent iron complex and its cellular uptake. , 2011, Inorganic chemistry.

[281]  Ji Hee Han,et al.  Dual-color imaging of magnesium/calcium ion activities with two-photon fluorescent probes. , 2012, Analytical chemistry.

[282]  Sung-Jin Park,et al.  Diversity oriented fluorescence library approach (DOFLA) for live cell imaging probe development. , 2014, Accounts of chemical research.

[283]  S. Yao,et al.  A switchable two-photon membrane tracer capable of imaging membrane-associated protein tyrosine phosphatase activities. , 2013, Angewandte Chemie.

[284]  C. Heo,et al.  A Golgi-localized two-photon probe for imaging zinc ions. , 2015, Chemical communications.

[285]  Chulhun Kang,et al.  A self-calibrating bipartite viscosity sensor for mitochondria. , 2013, Journal of the American Chemical Society.

[286]  Elizabeth M. Nolan,et al.  Organelle-specific zinc detection using zinpyr-labeled fusion proteins in live cells. , 2008, Journal of the American Chemical Society.

[287]  Ryan E. Mills,et al.  Classical Nuclear Localization Signals: Definition, Function, and Interaction with Importin α* , 2007, Journal of Biological Chemistry.

[288]  B. Tang,et al.  Real-time monitoring of the mitophagy process by a photostable fluorescent mitochondrion-specific bioprobe with AIE characteristics. , 2015, Chemical communications.

[289]  Amy E. Palmer,et al.  Fluorescent Sensors for Measuring Metal Ions in Living Systems , 2014, Chemical reviews.

[290]  Jianhua Zhang,et al.  Lysosomal function in macromolecular homeostasis and bioenergetics in Parkinson's disease , 2010, Molecular Neurodegeneration.

[291]  H. Vogel,et al.  Labeling of fusion proteins of O6-alkylguanine-DNA alkyltransferase with small molecules in vivo and in vitro. , 2004, Methods.

[292]  Jong Seung Kim,et al.  Chromogenic/Fluorogenic Ensemble Chemosensing Systems. , 2015, Chemical reviews.

[293]  E. Arriaga,et al.  Within the cell: analytical techniques for subcellular analysis , 2005, Analytical and bioanalytical chemistry.

[294]  Chang Su Lim,et al.  Ratiometric detection of mitochondrial thiols with a two-photon fluorescent probe. , 2011, Journal of the American Chemical Society.

[295]  Jiangli Fan,et al.  Fluorescence imaging lysosomal changes during cell division and apoptosis observed using Nile Blue based near-infrared emission. , 2014, Chemical communications.

[296]  W. Martin,et al.  Evolutionary biology: Essence of mitochondria , 2003, Nature.

[297]  B. Tang,et al.  A near-infrared ratiometric fluorescent probe for rapid and highly sensitive imaging of endogenous hydrogen sulfide in living cells , 2013 .

[298]  G. Lur,et al.  Ribosome-free Terminals of Rough ER Allow Formation of STIM1 Puncta and Segregation of STIM1 from IP3 Receptors , 2009, Current Biology.

[299]  Guy A Rutter,et al.  Genetically encoded FRET sensors to monitor intracellular Zn2+ homeostasis , 2009, Nature Methods.

[300]  Juan Tang,et al.  A sensitive and quantitative autolysosome probe for detecting autophagic activity in live and prestained fixed cells , 2013, Autophagy.

[301]  Ryan J H West,et al.  Oxidative stress and autophagy , 2012, Autophagy.

[302]  Yan-hong Liu,et al.  A mitochondria-targeted colorimetric and ratiometric fluorescent probe for biological SO2 derivatives in living cells. , 2015, Chemical communications.

[303]  B. Cho,et al.  Two-photon probes for intracellular free metal ions, acidic vesicles, and lipid rafts in live tissues. , 2009, Accounts of chemical research.

[304]  E. Gratton,et al.  Lipid--protein interactions revealed by two-photon microscopy and fluorescence correlation spectroscopy. , 2005, Accounts of chemical research.

[305]  Srinivasa R. Mandalapu,et al.  New rhodamine nitroxide based fluorescent probes for intracellular hydroxyl radical identification in living cells. , 2012, Organic letters.

[306]  D. Eide Zinc transporters and the cellular trafficking of zinc. , 2006, Biochimica et biophysica acta.

[307]  Qiao Jiang,et al.  Visualization of the intracellular location and stability of DNA origami with a label-free fluorescent probe. , 2012, Chemical communications.

[308]  Young-Tae Chang,et al.  Discovery of a green DNA probe for live-cell imaging. , 2010, Chemical communications.

[309]  T. Nishio,et al.  Multicolor imaging of endoplasmic reticulum-located esterase as a prodrug activation enzyme. , 2014, ACS medicinal chemistry letters.

[310]  Kate S. Carroll,et al.  Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery , 2013, Chemical reviews.

[311]  Lin Yuan,et al.  A unique approach to development of near-infrared fluorescent sensors for in vivo imaging. , 2012, Journal of the American Chemical Society.

[312]  Xi-jun Wang,et al.  Modern analytical techniques in metabolomics analysis. , 2012, The Analyst.

[313]  Young‐Tae Chang,et al.  Control of muscle differentiation by a mitochondria-targeted fluorophore. , 2010, Journal of the American Chemical Society.

[314]  Lingxin Chen,et al.  Visualization of nitroxyl (HNO) in vivo via a lysosome-targetable near-infrared fluorescent probe. , 2014, Chemical communications.

[315]  P. Mozdziak,et al.  Hoechst fluorescence intensity can be used to separate viable bromodeoxyuridine-labeled cells from viable non-bromodeoxyuridine-labeled cells. , 2000, Cytometry.

[316]  Y. Sasaki,et al.  Fluorescent sensor responsive to local viscosity and its application to the imaging of liquid-ordered domain in lipid membranes. , 2008, Colloids and surfaces. B, Biointerfaces.

[317]  Young‐Tae Chang,et al.  A Multisite-Binding Switchable Fluorescent Probe for Monitoring Mitochondrial ATP Level Fluctuation in Live Cells. , 2016, Angewandte Chemie.

[318]  J. Luzio,et al.  Lysosome-endosome fusion and lysosome biogenesis. , 2000, Journal of cell science.

[319]  M. Murphy,et al.  Slip and leak in mitochondrial oxidative phosphorylation. , 1989, Biochimica et biophysica acta.

[320]  Yu Qin,et al.  A long wavelength hydrophobic probe for intracellular lipid droplets. , 2014, The Analyst.

[321]  S. Passarella,et al.  The role of metal ions in the transport of substrates in mitochondria , 1973, FEBS letters.

[322]  R. Zenobi,et al.  Analytical techniques for single-cell metabolomics: state of the art and trends , 2010, Analytical and bioanalytical chemistry.

[323]  K. Jolliffe,et al.  Fluorescent and colorimetric chemosensors for pyrophosphate. , 2015, Chemical Society reviews.

[324]  Guoping Li,et al.  A ratiometric and targetable fluorescent sensor for quantification of mitochondrial zinc ions. , 2012, Chemistry.

[325]  Maya Shvartsman,et al.  Intracellular labile iron pools as direct targets of iron chelators: a fluorescence study of chelator action in living cells. , 2005, Blood.

[326]  Kedong Song,et al.  Ratiometric fluorescence imaging of lysosomal Zn2+ release under oxidative stress in neural stem cells. , 2014, Biomaterials science.

[327]  Peter Lipp,et al.  Calcium - a life and death signal , 1998, Nature.

[328]  Peng Li,et al.  Reversible near-infrared fluorescent probe introducing tellurium to mimetic glutathione peroxidase for monitoring the redox cycles between peroxynitrite and glutathione in vivo. , 2013, Journal of the American Chemical Society.

[329]  Alexandra T. Wrobel,et al.  A far-red emitting probe for unambiguous detection of mobile zinc in acidic vesicles and deep tissue , 2015, Chemical science.

[330]  William J. Pavan,et al.  Lysosomal Targeting with Stable and Sensitive Fluorescent Probes (Superior LysoProbes): Applications for Lysosome Labeling and Tracking during Apoptosis , 2015, Scientific Reports.

[331]  R. Nakamoto,et al.  The rotary mechanism of the ATP synthase. , 2008, Archives of biochemistry and biophysics.

[332]  Fengling Song,et al.  An effective minor groove binder as a red fluorescent marker for live-cell DNA imaging and quantification. , 2011, Angewandte Chemie.

[333]  Derek Toomre,et al.  Super-resolution imaging of the Golgi in live cells with a bioorthogonal ceramide probe. , 2014, Angewandte Chemie.

[334]  L. Staehelin,et al.  A three-stage model of Golgi structure and function , 2013, Histochemistry and Cell Biology.

[335]  L. C. Moore,et al.  Nuclear envelope permeability , 1975, Nature.

[336]  Jiangli Fan,et al.  An off-on COX-2-specific fluorescent probe: targeting the Golgi apparatus of cancer cells. , 2013, Journal of the American Chemical Society.

[337]  W. Neupert,et al.  Protein transport into mitochondria. , 2000, Current opinion in microbiology.

[338]  Lin Yang,et al.  Microtubule-targetable fluorescent probe: site-specific detection and super-resolution imaging of ultratrace tubulin in microtubules of living cancer cells. , 2015, Analytical chemistry.

[339]  D. Spring,et al.  A lysosome-targetable fluorescent probe for imaging hydrogen sulfide in living cells. , 2013, Organic letters.

[340]  V. Prasad,et al.  Secretory pathway stress responses as possible mechanisms of disease involving Golgi Ca2+ pump dysfunction. , 2011, BioFactors.

[341]  F. Petrat,et al.  Assessment of Chelatable Mitochondrial Iron by Using Mitochondrion‐Selective Fluorescent Iron Indicators with Different Iron‐Binding Affinities , 2007, Chembiochem : a European journal of chemical biology.

[342]  G. Cecchini,et al.  Function and structure of complex II of the respiratory chain. , 2003, Annual review of biochemistry.

[343]  J. St-Pierre,et al.  Going with the flow or life in the fast lane: contrasting mitochondrial responses to thermal change. , 2002, The Journal of experimental biology.

[344]  Y. Harada,et al.  Intracellular temperature mapping with a fluorescent polymeric thermometer and fluorescence lifetime imaging microscopy , 2012, Nature Communications.

[345]  Peter Lipp,et al.  Cooking with Calcium: The Recipes for Composing Global Signals from Elementary Events , 1997, Cell.

[346]  B. Goodman Transport of small molecules across cell membranes: water channels and urea transporters. , 2002, Advances in physiology education.

[347]  A. V. Villamil Giraldo,et al.  Lysosomotropic agents: impact on lysosomal membrane permeabilization and cell death. , 2014, Biochemical Society transactions.

[348]  Allegra T. Aron,et al.  Synthetic fluorescent probes for studying copper in biological systems. , 2015, Chemical Society reviews.

[349]  G. Ning,et al.  FRET-based ratiometric fluorescent probes for selective Fe3+ sensing and their applications in mitochondria. , 2013, Dalton transactions.

[350]  D. Winge,et al.  Metal Ion availability in mitochondria , 2007, BioMetals.

[351]  M. Balakirev,et al.  Effect of the triaminopyridine flupirtine on calcium uptake, membrane potential and ATP synthesis in rat heart mitochondria , 1998, British journal of pharmacology.

[352]  Christopher J Chang,et al.  Organelle-targetable fluorescent probes for imaging hydrogen peroxide in living cells via SNAP-Tag protein labeling. , 2010, Journal of the American Chemical Society.

[353]  W. Bushnell,et al.  Pontentiometric cyanine dyes are sensitive probes for mitochondria in intact plant cells : kinetin enhances mitochondrial fluorescence. , 1987, Plant physiology.

[354]  Jong Seung Kim,et al.  The role of copper ions in pathophysiology and fluorescent sensors for the detection thereof. , 2015, Chemical communications.

[355]  Kaibo Zheng,et al.  FRET-based small-molecule fluorescent probes: rational design and bioimaging applications. , 2013, Accounts of chemical research.

[356]  J. Eaton,et al.  Intralysosomal iron: a major determinant of oxidant-induced cell death. , 2003, Free radical biology & medicine.

[357]  Jong Hwa Jung,et al.  Enhanced NIR radiation-triggered hyperthermia by mitochondrial targeting. , 2015, Journal of the American Chemical Society.

[358]  Keiko Kuwata,et al.  Hoechst tagging: a modular strategy to design synthetic fluorescent probes for live-cell nucleus imaging. , 2014, Chemical communications.

[359]  B. Liu,et al.  Biocompatible Flavone-Based Fluorogenic Probes for Quick Wash-Free Mitochondrial Imaging in Living Cells , 2014, ACS applied materials & interfaces.

[360]  E. Gratton,et al.  Visualizing lipid structure and raft domains in living cells with two-photon microscopy , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[361]  Lingxin Chen,et al.  Near-infrared fluorescent probe for imaging mitochondrial hydrogen polysulfides in living cells and in vivo. , 2015, Analytical chemistry.

[362]  Yingying Huo,et al.  A mitochondria-targetable fluorescent probe for dual-channel NO imaging assisted by intracellular cysteine and glutathione. , 2014, Journal of the American Chemical Society.

[363]  L. Vidali,et al.  Rab2 GTPase Regulates Vesicle Trafficking between the Endoplasmic Reticulum and the Golgi Bodies and Is Important to Pollen Tube Growth Online version contains Web-only data. Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.000836. , 2002, The Plant Cell Online.

[364]  O. Wolfbeis,et al.  Targetable phosphorescent oxygen nanosensors for the assessment of tumor mitochondrial dysfunction by monitoring the respiratory activity. , 2014, Angewandte Chemie.

[365]  Ronald D Vale,et al.  The Molecular Motor Toolbox for Intracellular Transport , 2003, Cell.

[366]  M. Murphy,et al.  Selective targeting of bioactive compounds to mitochondria. , 1997, Trends in biotechnology.

[367]  S. Rhee,et al.  H2O2, a Necessary Evil for Cell Signaling , 2006, Science.

[368]  S. Arai,et al.  A TEMPO-conjugated fluorescent probe for monitoring mitochondrial redox reactions. , 2012, Chemical communications.

[369]  W. Tan,et al.  Engineering a subcellular targetable, red-emitting, and ratiometric fluorescent probe for Ca2+ and its bioimaging applications , 2010, Analytical and bioanalytical chemistry.

[370]  H. Crissman,et al.  Staining of DNA in live and fixed cells. , 1994, Methods in cell biology.

[371]  W. Cascio,et al.  Selective loading of Rhod 2 into mitochondria shows mitochondrial Ca2+ transients during the contractile cycle in adult rabbit cardiac myocytes. , 1997, Biochemical and biophysical research communications.

[372]  Ying Zhou,et al.  Fluorescent and colorimetric chemosensors for detection of nucleotides, FAD and NADH: highlighted research during 2004-2010. , 2011, Chemical Society reviews.

[373]  Jeffrey P Krise,et al.  Lysosomal sequestration of amine-containing drugs: analysis and therapeutic implications. , 2007, Journal of pharmaceutical sciences.

[374]  Tullio Pozzan,et al.  Mitochondrial pH Monitored by a New Engineered Green Fluorescent Protein Mutant* , 2004, Journal of Biological Chemistry.

[375]  John R. Allen,et al.  A FRET-based indicator for imaging mitochondrial zinc ions. , 2011, Chemical communications.

[376]  Yi Xiao,et al.  A lysosome-targetable and two-photon fluorescent probe for monitoring endogenous and exogenous nitric oxide in living cells. , 2012, Journal of the American Chemical Society.

[377]  C. S. Lim,et al.  Detection of Near-membrane Calcium Ions in Live Tissues with a Two-Photon Fluorescent Probe , 2010 .

[378]  Luís M. S. Loura,et al.  Fluorescent membrane probes’ behavior in lipid bilayers: insights from molecular dynamics simulations , 2009, Biophysical Reviews.

[379]  C E Kung,et al.  Fluorescent molecular rotors: a new class of probes for tubulin structure and assembly. , 1989, Biochemistry.

[380]  Hong Wang,et al.  Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers , 2013, Journal of Hematology & Oncology.

[381]  H. Padh,et al.  Organelle targeting: third level of drug targeting , 2013, Drug design, development and therapy.

[382]  T. Hirayama,et al.  A highly selective turn-on fluorescent probe for iron(II) to visualize labile iron in living cells , 2013 .

[383]  K. Cheah,et al.  Cyanines as new fluorescent probes for DNA detection and two-photon excited bioimaging. , 2010, Organic letters.

[384]  B. Cho,et al.  Mitochondrial-Targeted Two-Photon Fluorescent Probes for Zinc Ions, H2O2, and Thiols in Living Tissues , 2013, Oxidative medicine and cellular longevity.

[385]  Jong Seung Kim,et al.  BODIPY/Nile-Red-Based Efficient FRET Pair: Selective Assay of Endoplasmic Reticulum Membrane Fluidity. , 2016, Chemistry, an Asian journal.

[386]  Juyoung Yoon,et al.  A ratiometric fluorescent probe based on a coumarin-hemicyanine scaffold for sensitive and selective detection of endogenous peroxynitrite. , 2015, Biosensors & bioelectronics.

[387]  Bryan C Dickinson,et al.  Mitochondrial-targeted fluorescent probes for reactive oxygen species. , 2010, Current opinion in chemical biology.

[388]  Donald Wlodkowic,et al.  ER-Golgi network--a future target for anti-cancer therapy. , 2009, Leukemia research.

[389]  Ping Li,et al.  A lysosomal-targeted fluorescent probe for detecting Cu2+ , 2012 .

[390]  Chii-Shiarng Chen,et al.  Phorbol ester induces elevated oxidative activity and alkalization in a subset of lysosomes , 2002, BMC Cell Biology.