title: Intracellular pH Modulates Autophagy and Mitophagy.
abstract: The specific autophagic elimination of mitochondria (mitophagy) plays the role of quality control for this organelle. Deregulation of mitophagy leads to an increased number of damaged mitochondria and triggers cell death. The deterioration of mitophagy has been hypothesized to underlie the pathogenesis of several neurodegenerative diseases, most notably Parkinson disease. Although some of the biochemical and molecular mechanisms of mitochondrial quality control are described in detail, physiological or pathological triggers of mitophagy are still not fully characterized. Here we show that the induction of mitophagy by the mitochondrial uncoupler FCCP is independent of the effect of mitochondrial membrane potential but dependent on acidification of the cytosol by FCCP. The ionophore nigericin also reduces cytosolic pH and induces PINK1/PARKIN-dependent and -independent mitophagy. The increase of intracellular pH with monensin suppresses the effects of FCCP and nigericin on mitochondrial degradation. Thus, a change in intracellular pH is a regulator of mitochondrial quality control.
authors.affiliation: From the Department of Intracellular Signaling, Institute of Cell Biophysics Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russian Federation and.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Berezhnov
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom.
authors.forename: Marc P M
authors.initials: MP
authors.lastname: Soutar
authors.affiliation: From the Department of Intracellular Signaling, Institute of Cell Biophysics Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russian Federation and.
authors.forename: Evgeniya I
authors.initials: EI
authors.lastname: Fedotova
authors.affiliation: From the Department of Intracellular Signaling, Institute of Cell Biophysics Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russian Federation and.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Frolova
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom.
authors.forename: Helene
authors.initials: H
authors.lastname: Plun-Favreau
authors.affiliation: From the Department of Intracellular Signaling, Institute of Cell Biophysics Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russian Federation and.
authors.forename: Valery P
authors.initials: VP
authors.lastname: Zinchenko
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, United Kingdom a.abramov@ucl.ac.uk.
authors.forename: Andrey Y
authors.initials: AY
authors.lastname: Abramov
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D063306:Mitophagy / Q000187:drug effects*; D011494:Protein Kinases / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D000099202:PTEN-Induced Putative Kinase
chemical_list: D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein
keywords: autophagy; intracellular pH; lysosome; mitochondria; mitophagy; neurodegeneration