Mitophagy and mitochondrial morphology in human melanoma-derived cells post exposure to simulated sunlight

Purpose: To assess changes in mitochondrial morphology and mitophagy induced by simulated sunlight irradiation (SSI) and how these changes are modulated by mitochondrial activity and energy source. Materials and methods: Human malignant amelanotic melanoma A375 cells were pre-treated with either a mitochondrial activity enhancer, uncoupler or were either melanin or glutamine supplemented/starved for 4 hours pre-exposure to sunlight. A Q-Sun Solar Simulator (Q-Lab, Homestead, FL, USA) was employed to expose cells to simulated sunlight. Confocal microscopy imaging of A375 cells co-loaded with mitochondria and lysosome-specific fluorescent dyes was used to identify these organelles and predict mitophagic events. Results: SSI induces pronounced changes in mitochondrial dynamics and mitophagy in exposed skin cells compared to control and these effects were modified by both glutamine and melanin. Conclusions: Mitochondrial dynamics and rate of mitophagy in melanoma cells are sensitive to even short bursts of environmentally relevant SSI. Mitochondrial dynamics, and its modulation, may also play a role in mitophagy regulation, cell survival and proliferation post SSI.

[1]  Robert Clarke,et al.  Guidelines for the use and interpretation of assays for monitoring autophagy , 2012 .

[2]  C. Chu,et al.  Mitochondrial kinases in Parkinson's disease: converging insights from neurotoxin and genetic models. , 2009, Mitochondrion.

[3]  N. Camougrand,et al.  Glutathione participates in the regulation of mitophagy in yeast , 2009, Autophagy.

[4]  Y. Ohsumi,et al.  Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. , 2009, Developmental cell.

[5]  N. Mizushima,et al.  A receptor for eating mitochondria. , 2009, Developmental cell.

[6]  J. Menéndez,et al.  Autophagy Facilitates the Development of Breast Cancer Resistance to the Anti-HER2 Monoclonal Antibody Trastuzumab , 2009, PloS one.

[7]  K. Heidenreich,et al.  Insulin-like Growth Factor-I Prevents the Accumulation of Autophagic Vesicles and Cell Death in Purkinje Neurons by Increasing the Rate of Autophagosome-to-lysosome Fusion and Degradation* , 2009, The Journal of Biological Chemistry.

[8]  Jean-Claude Martinou,et al.  SLP‐2 is required for stress‐induced mitochondrial hyperfusion , 2009, The EMBO journal.

[9]  S. Sheu,et al.  Morphological dynamics of mitochondria--a special emphasis on cardiac muscle cells. , 2009, Journal of molecular and cellular cardiology.

[10]  R. Malli,et al.  Mitochondrial protein phosphorylation: instigator or target of lipotoxicity? , 2009, Trends in Endocrinology & Metabolism.

[11]  Yongqiang Chen,et al.  Regulation of autophagy by reactive oxygen species (ROS): implications for cancer progression and treatment. , 2009, Antioxidants & redox signaling.

[12]  P. Navas,et al.  Coenzyme Q deficiency triggers mitochondria degradation by mitophagy , 2009, Autophagy.

[13]  J. Andersen,et al.  Ordered Organelle Degradation during Starvation-induced Autophagy*S , 2008, Molecular & Cellular Proteomics.

[14]  K. Yu,et al.  DE-71-induced apoptosis involving intracellular calcium and the Bax-mitochondria-caspase protease pathway in human neuroblastoma cells in vitro. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[15]  John L Cleveland,et al.  Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes , 2008, Autophagy.

[16]  Min Wu,et al.  Fission and selective fusion govern mitochondrial segregation and elimination by autophagy , 2008, The EMBO journal.

[17]  R. Deberardinis,et al.  The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. , 2008, Cell metabolism.

[18]  A. Calastretti,et al.  Cell survival under nutrient stress is dependent on metabolic conditions regulated by Akt and not by autophagic vacuoles. , 2007, Cellular signalling.

[19]  J. Vicencio,et al.  Cell Cycle-Dependent Induction of Autophagy, Mitophagy and Reticulophagy , 2007, Cell cycle.

[20]  Nicola Zamboni,et al.  Deficiency in glutamine but not glucose induces MYC-dependent apoptosis in human cells , 2007, The Journal of cell biology.

[21]  S. Rodríguez-Enríquez,et al.  Selective degradation of mitochondria by mitophagy. , 2007, Archives of biochemistry and biophysics.

[22]  M. Lotem,et al.  Ultraviolet radiation and cutaneous carcinogenesis. , 2007, Current problems in dermatology.

[23]  T. Langer,et al.  Studying proteolysis within mitochondria. , 2007, Methods in molecular biology.

[24]  F. Lang,et al.  Cell volume regulatory ion channels in cell proliferation and cell death. , 2007, Methods in enzymology.

[25]  U. Brunk,et al.  Mitochondrial damage and intralysosomal degradation in cellular aging. , 2006, Molecular aspects of medicine.

[26]  M. Norenberg,et al.  Glutamine: A Trojan horse in ammonia neurotoxicity , 2006, Hepatology.

[27]  Pei Wang,et al.  Glutamine granule-supplemented enteral nutrition maintains immunological function in severely burned patients. , 2006, Burns : journal of the International Society for Burn Injuries.

[28]  E. Bergamini,et al.  Stimulation of macroautophagy can rescue older cells from 8-OHdG mtDNA accumulation: a safe and easy way to meet goals in the SENS agenda. , 2006, Rejuvenation research.

[29]  M. Birch-Machin,et al.  The role of mitochondria in ageing and carcinogenesis , 2006, Clinical and experimental dermatology.

[30]  S. Rodríguez-Enríquez,et al.  Tracker Dyes to Probe Mitochondrial Autophagy (Mitophagy) in Rat Hepatocytes , 2006, Autophagy.

[31]  K. Mckenney,et al.  Mitochondrial DNA as a potential tool for early cancer detection , 2006, Human Genomics.

[32]  M. Wernli,et al.  Role of apoptosis in basal cell and squamous cell carcinoma formation. , 2005, Immunology letters.

[33]  Ana Maria Cuervo,et al.  Autophagy and Aging: The Importance of Maintaining "Clean" Cells , 2005, Autophagy.

[34]  J. Lemasters.  Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. , 2005, Rejuvenation research.

[35]  R. Scolyer,et al.  In vivo and ex vivo proton MR spectroscopy of primary and secondary melanoma. , 2005, European journal of radiology.

[36]  K. Wittern,et al.  The creatine kinase system in human skin: protective effects of creatine against oxidative and UV damage in vitro and in vivo. , 2005, The Journal of investigative dermatology.

[37]  Yasunori Hayashi,et al.  The Importance of Dendritic Mitochondria in the Morphogenesis and Plasticity of Spines and Synapses , 2004, Cell.

[38]  John J Lemasters,et al.  Role of mitochondrial permeability transition pores in mitochondrial autophagy. , 2004, The international journal of biochemistry & cell biology.

[39]  V. Skulachev,et al.  Selective elimination of mitochondria from living cells induced by inhibitors of bioenergetic functions. , 2004, Biochemical Society transactions.

[40]  Da-Woon Jung,et al.  Identification of compounds that bind mitochondrial F1F0 ATPase by screening a triazine library for correction of albinism. , 2004, Chemistry & biology.

[41]  J. Eaton,et al.  Aging of Cardiac Myocytes in Culture: Oxidative Stress, Lipofuscin Accumulation, and Mitochondrial Turnover , 2004, Annals of the New York Academy of Sciences.

[42]  K. Kirkegaard,et al.  Cellular autophagy: surrender, avoidance and subversion by microorganisms , 2004, Nature Reviews Microbiology.

[43]  J. Vasiliev,et al.  Thread-grain transition of mitochondrial reticulum as a step of mitoptosis and apoptosis , 2004, Molecular and Cellular Biochemistry.

[44]  K. Dold,et al.  Effect of the dose of ultraviolet radiation on the pigment formation by human melanocytes in vitro , 2004, Archives of Dermatological Research.

[45]  J. Eaton,et al.  Mitochondrial recycling and aging of cardiac myocytes: the role of autophagocytosis , 2003, Experimental Gerontology.

[46]  S. Grimm,et al.  The tumor suppressor cybL, a component of the respiratory chain, mediates apoptosis induction. , 2003, Molecular biology of the cell.

[47]  M. Ueda,et al.  UV-induced skin damage. , 2003, Toxicology.

[48]  K. Mihara,et al.  Regulation of mitochondrial morphology by membrane potential, and DRP1-dependent division and FZO1-dependent fusion reaction in mammalian cells. , 2003, Biochemical and biophysical research communications.

[49]  P. Frachon,et al.  Mitochondrial fusion in human cells is efficient, requires the inner membrane potential, and is mediated by mitofusins. , 2002, Molecular biology of the cell.

[50]  O. Tirosh,et al.  Membrane depolarization of isolated rat liver mitochondria attenuates permeability transition pore opening and oxidant production. , 2002, Antioxidants & redox signaling.

[51]  L. Naldi,et al.  The epidemiology of skin cancer , 2002, The British journal of dermatology.

[52]  S. Werner,et al.  Creatine kinase and creatine transporter in normal, wounded, and diseased skin. , 2002, The Journal of investigative dermatology.

[53]  Y. Naito,et al.  α-Phenyl-N-tert-Butylnitrone Provides Protection from Dextran Sulfate Sodium-Induced Colitis in Mice , 2002 .

[54]  M. Blumenberg,et al.  Rays and arrays: the transcriptional program in the response of human epidermal keratinocytes to UVB illumination , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[55]  S. Frank,et al.  The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. , 2001, Developmental cell.

[56]  M. Medina,et al.  Glutamine and cancer. , 2001, The Journal of nutrition.

[57]  M. Yaar,et al.  Solar simulated irradiation modulates gene expression and activity of antioxidant enzymes in cultured human dermal fibroblasts , 2001, Experimental dermatology.

[58]  L. Bindoff,et al.  Mitochondrial Respiratory Chain Disorders , 2001 .

[59]  F. Al-Khodairy,et al.  p53 is dispensable for UV-induced cell cycle arrest at late G(1) in mammalian cells. , 2001, Carcinogenesis.

[60]  T. Wallimann,et al.  Mitochondrial Creatine Kinase in Contact Sites: Interaction with Porin and Adenine Nucleotide Translocase, Role in Permeability Transition and Sensitivity to Oxidative Damage , 2001, Neurosignals.

[61]  S. Alper,et al.  Polarization of Na+/H+ and Cl−/Hco 3 − Exchangers in Migrating Renal Epithelial Cells , 2000, The Journal of general physiology.

[62]  R. Buscà,et al.  Cyclic AMP a key messenger in the regulation of skin pigmentation. , 2000, Pigment cell research.

[63]  A. Schapira,et al.  Mitochondrial respiratory chain disorders I: mitochondrial DNA defects , 2000, The Lancet.

[64]  K. Gilmore,et al.  The use of chloromethyl-X-rosamine (Mitotracker red) to measure loss of mitochondrial membrane potential in apoptotic cells is incompatible with cell fixation. , 1999, Cytometry.

[65]  E. Land,et al.  Free radical scavenging properties of melanin interaction of eu- and pheo-melanin models with reducing and oxidising radicals. , 1999, Free radical biology & medicine.

[66]  L. Liotta,et al.  Cyclocreatine inhibits stimulated motility in tumor cells possessing creatine kinase , 1998, International Journal of Cancer.

[67]  D. Brenner,et al.  The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. , 1998, Biochimica et biophysica acta.

[68]  José Luis de la Pompa,et al.  Differential Requirement for Caspase 9 in Apoptotic Pathways In Vivo , 1998, Cell.

[69]  H. Ananthaswamy,et al.  Mechanisms of induction of skin cancer by UV radiation. , 1997, Frontiers in bioscience : a journal and virtual library.

[70]  S. Nigam,et al.  Perturbations in maturation of secretory proteins and their association with endoplasmic reticulum chaperones in a cell culture model for epithelial ischemia. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[71]  A. Vercesi,et al.  Effect of Inorganic Phosphate Concentration on the Nature of Inner Mitochondrial Membrane Alterations Mediated by Ca Ions , 1996, The Journal of Biological Chemistry.

[72]  A E Vercesi,et al.  Effect of inorganic phosphate concentration on the nature of inner mitochondrial membrane alterations mediated by Ca2+ ions. A proposed model for phosphate-stimulated lipid peroxidation. , 1996, The Journal of biological chemistry.

[73]  D. Häussinger,et al.  Regulation of cell function by the cellular hydration state. , 1994, The American journal of physiology.

[74]  L. Baggetto,et al.  Deviant energetic metabolism of glycolytic cancer cells. , 1992, Biochimie.

[75]  M. Schindler,et al.  Alkalinization of the lysosomes is correlated with ras transformation of murine and human fibroblasts. , 1990, The Journal of biological chemistry.

[76]  P. Seglen,et al.  Energy dependence of different steps in the autophagic-lysosomal pathway. , 1989, The Journal of biological chemistry.

[77]  V. Skulachev,et al.  Coupling membranes as energy-transmitting cables. I. Filamentous mitochondria in fibroblasts and mitochondrial clusters in cardiomyocytes , 1988, The Journal of cell biology.

[78]  G. Mortimore,et al.  The lysosomal pathway of intracellular proteolysis in liver: regulation by amino acids. , 1986, Advances in enzyme regulation.

[79]  L. Reitzer,et al.  The continuous growth of vertebrate cells in the absence of sugar. , 1981, The Journal of biological chemistry.

[80]  R. L. Hawkins,et al.  Lactate: A major product of glutamine metabolism by human diploid fibroblasts , 1980, Journal of cellular physiology.

[81]  H. Morris,et al.  The role of glutamine in the oxidative metabolism of malignant cells. , 1972, Cancer research.