UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Intracellular pH Modulates Autophagy and Mitophagy

Berezhnov, AV; Soutar, MPM; Fedotova, EI; Frolova, MS; Plun-Favreau, H; Zinchenko, VP; Abramov, AY; (2016) Intracellular pH Modulates Autophagy and Mitophagy. Journal of Biological Chemistry , 291 (16) pp. 8701-8708. 10.1074/jbc.M115.691774. Green open access

[thumbnail of Abramov_zbc8701.pdf]
Preview
Text
Abramov_zbc8701.pdf - Published Version

Download (3MB) | Preview

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.

Type: Article
Title: Intracellular pH Modulates Autophagy and Mitophagy
Open access status: An open access version is available from UCL Discovery
DOI: 10.1074/jbc.M115.691774
Publisher version: http://dx.doi.org/10.1074/jbc.M115.691774
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, autophagy, lysosome, mitochondria, mitophagy, neurodegeneration, intracellular pH, PARKINSONS-DISEASE, INDUCE MITOPHAGY, KINASE PINK1, MITOCHONDRIA, P62/SQSTM1, RETICULUM, LYSOSOME, RELEASE, STRESS, MANNER
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1479660
Downloads since deposit
122Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item