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Association and dissociation between the mitochondrial Far complex and Atg32 regulate mitophagy

Aleksei Innokentev1, Kentaro Furukawa1, Tomoyuki Fukuda1

  • 1Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Elife
|December 15, 2020
PubMed

Insights

The Far complex, including Ppg1, inhibits mitophagy by dephosphorylating Atg32. Its dissociation from Atg32 is crucial for mitophagy regulation in yeast.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitophagy is vital for maintaining mitochondrial health.
  • Phosphorylation of Atg32 by casein kinase 2 is essential for yeast mitophagy.
  • The STRIPAK complex, comprising Ppg1 and the Far complex, counteracts Atg32 phosphorylation, but its mechanism is unclear.

Purpose of the Study:

  • To elucidate the mechanism by which the Ppg1-Far complex regulates mitophagy.
  • To investigate the distinct roles of Far complex subpopulations in mitochondria and endoplasmic reticulum.
  • To understand the interaction between the Far complex and the mitophagy receptor Atg32.

Main Methods:

  • Subcellular localization studies to identify Far complex subpopulations.
  • Biochemical assays to analyze Ppg1-Far complex integrity and Atg32 interaction.
  • Genetic manipulation (artificial tethering) to assess mitophagy regulation.

Main Results:

  • Two Far complex subpopulations were identified in mitochondria and ER, with distinct functions.
  • The mitochondrial subpopulation inhibits mitophagy via Atg32 dephosphorylation.
  • The Ppg1-Far complex preferentially binds phosphorylated Atg32, and this interaction decreases upon mitophagy induction.

Conclusions:

  • Ppg1-mediated Far complex formation and its subsequent dissociation from Atg32 are critical for mitophagy control.
  • Mitochondrial and ER-localized Far complexes have divergent roles in cellular signaling and mitophagy.
  • Understanding this regulation provides insights into mitochondrial homeostasis.
Keywords:
Atg32Far complexPpg1S. cerevisiaeSTRIPAK complexautophagycell biologymitophagy

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