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In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice
08:40

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice

Published on: November 22, 2017

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Intracellular pH Modulates Autophagy and Mitophagy

Alexey V Berezhnov1, Marc P M Soutar2, Evgeniya I Fedotova1

  • 1From the Department of Intracellular Signaling, Institute of Cell Biophysics Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russian Federation and.

The Journal of Biological Chemistry
|February 20, 2016
PubMed

Insights

Cytosolic pH changes, not mitochondrial membrane potential, regulate mitophagy. This finding reveals a new mechanism controlling mitochondrial quality and may impact neurodegenerative disease research.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Mitochondrial Dynamics

Background:

  • Mitophagy, the selective autophagic removal of mitochondria, is crucial for cellular quality control.
  • Dysfunctional mitophagy is linked to neurodegenerative diseases like Parkinson's disease.
  • Triggers for mitophagy are not fully understood, hindering therapeutic development.

Purpose of the Study:

  • To investigate the role of cytosolic pH in regulating mitophagy.
  • To determine if mitochondrial membrane potential or cytosolic pH is the primary trigger for mitophagy induction.

Main Methods:

  • Utilized the mitochondrial uncoupler FCCP to induce mitophagy.
  • Employed the ionophore nigericin to alter cytosolic pH.
  • Used monensin to manipulate intracellular pH levels.
  • Assessed mitophagy induction and its dependence on PINK1/PARKIN pathways.

Main Results:

  • FCCP-induced mitophagy is independent of mitochondrial membrane potential but dependent on cytosolic acidification.
  • Nigericin also induces mitophagy, correlating with reduced cytosolic pH.
  • Elevating intracellular pH with monensin inhibits FCCP- and nigericin-induced mitophagy.
  • Both PINK1/PARKIN-dependent and -independent mitophagy pathways are affected by pH changes.

Conclusions:

  • Intracellular pH is a critical regulator of mitochondrial quality control via mitophagy.
  • Cytosolic acidification, rather than changes in mitochondrial membrane potential, can trigger mitophagy.
  • These findings offer new insights into the pathogenesis of neurodegenerative diseases and potential therapeutic targets.
Keywords:
autophagyintracellular pHlysosomemitochondriamitophagyneurodegeneration

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