Development of a Chemogenetic Approach to Manipulate Intracellular pH

Chemogenetic Operation of iNTRacellular prOton Levels (pH-Control) is a novel substrate-based enzymatic method that enables precise spatiotemporal control of ultralocal acidification in cultured cell lines and primary neurons. The genetically encoded biosensor SypHer3s showed that pH-Control effectively acidifies cytosolic, mitochondrial, and nuclear pH exclusively in the presence of β-chloro-d-alanine in living cells in a concentration-dependent manner. The pH-Control approach is promising for investigating the ultralocal pH imbalance associated with many diseases.

[1]  K. Na,et al.  Intracellular pH-Regulating Nanoparticles to Improve Anticancer Drug Efficacy for Cancer Treatment. , 2022, Biomacromolecules.

[2]  Libo Zhao,et al.  Advanced tools and methods for single-cell surgery , 2022, Microsystems & nanoengineering.

[3]  M. Argentina,et al.  Intracellular pH Control by Membrane Transport in Mammalian Cells. Insights Into the Selective Advantages of Functional Redundancy , 2022, Frontiers in Molecular Biosciences.

[4]  Emrah Eroğlu,et al.  Chemogenetic approaches to dissect the role of H2O2 in redox-dependent pathways using genetically encoded biosensors. , 2022, Biochemical Society transactions.

[5]  D. Bers,et al.  Beat-to-beat dynamic regulation of intracellular pH in cardiomyocytes , 2021, iScience.

[6]  T. Michel,et al.  Chemogenetic Approaches to Probe Redox Pathways: Implications for Cardiovascular Pharmacology and Toxicology. , 2021, Annual review of pharmacology and toxicology.

[7]  K. A. White,et al.  An Optogenetic Tool to Raise Intracellular pH in Single Cells and Drive Localized Membrane Dynamics , 2021, bioRxiv.

[8]  D. Rusakov,et al.  Astrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle , 2020, Nature Communications.

[9]  Pawel Swietach,et al.  Evidence-based guidelines for controlling pH in mammalian live-cell culture systems , 2019, Communications Biology.

[10]  E. Ruppin,et al.  Systems analysis of intracellular pH vulnerabilities for cancer therapy , 2018, Nature Communications.

[11]  I. Yampolsky,et al.  SypHer3s: a genetically encoded fluorescent ratiometric probe with enhanced brightness and an improved dynamic range. , 2018, Chemical communications.

[12]  Michael Z. Lin,et al.  Fast two-photon imaging of subcellular voltage dynamics in neuronal tissue with genetically encoded indicators , 2017, eLife.

[13]  Jong Seung Kim,et al.  Fluorescent bioimaging of pH: from design to applications. , 2017, Chemical Society reviews.

[14]  G. Orive,et al.  Cellular acidification as a new approach to cancer treatment and to the understanding and therapeutics of neurodegenerative diseases. , 2017, Seminars in cancer biology.

[15]  G. Prosser,et al.  Glutamate Racemase Is the Primary Target of β-Chloro-d-Alanine in Mycobacterium tuberculosis , 2016, Antimicrobial Agents and Chemotherapy.

[16]  D. Barber,et al.  Increased H+ efflux is sufficient to induce dysplasia and necessary for viability with oncogene expression , 2015, eLife.

[17]  S. Bisht,et al.  Structural and Mutational Studies on Substrate Specificity and Catalysis of Salmonella typhimurium D-Cysteine Desulfhydrase , 2012, PloS one.

[18]  L. Huc,et al.  Alterations of intracellular pH homeostasis in apoptosis: origins and roles , 2004, Cell Death and Differentiation.

[19]  B. Masereel,et al.  An overview of inhibitors of Na(+)/H(+) exchanger. , 2003, European journal of medicinal chemistry.

[20]  D. Thwaites,et al.  Structure, function and immunolocalization of a proton‐coupled amino acid transporter (hPAT1) in the human intestinal cell line Caco‐2 , 2003, The Journal of physiology.

[21]  Sergio Grinstein,et al.  Sensors and regulators of intracellular pH , 2010, Nature Reviews Molecular Cell Biology.