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

Aleksei Innokentev | Kentaro Furukawa | Tomoyuki Fukuda | Tetsu Saigusa | Keiichi Inoue | Shun-Ichi Yamashita | Tomotake Kanki
eLife | 2020

Mitophagy plays an important role in mitochondrial homeostasis. In yeast, the phosphorylation of the mitophagy receptor Atg32 by casein kinase 2 is essential for mitophagy. This phosphorylation is counteracted by the yeast equivalent of the STRIPAK complex consisting of the PP2A-like protein phosphatase Ppg1 and Far3-7-8-9-10-11 (Far complex), but the underlying mechanism remains elusive. Here we show that two subpopulations of the Far complex reside in the mitochondria and endoplasmic reticulum, respectively, and play distinct roles; the former inhibits mitophagy via Atg32 dephosphorylation, and the latter regulates TORC2 signaling. Ppg1 and Far11 form a subcomplex, and Ppg1 activity is required for the assembling integrity of Ppg1-Far11-Far8. The Far complex preferentially interacts with phosphorylated Atg32, and this interaction is weakened by mitophagy induction. Furthermore, the artificial tethering of Far8 to Atg32 prevents mitophagy. Taken together, the Ppg1-mediated Far complex formation and its dissociation from Atg32 are crucial for mitophagy regulation.

Pubmed ID: 33317697

Associated grants

  • Agency: Japan Society for the Promotion of Science, International
    Id: 19K22419
  • Agency: Japan Society for the Promotion of Science, International
    Id: 19H05712
  • Agency: Japan Society for the Promotion of Science, International
    Id: 18H04858
  • Agency: Japan Society for the Promotion of Science, International
    Id: 18H04691
  • Agency: Japan Society for the Promotion of Science, International
    Id: 17H03671
  • Agency: Japan Society for the Promotion of Science, International
    Id: 18K06129
  • Agency: Japan Agency for Medical Research and Development, International
    Id: JP18gm6110013h0001
  • Agency: Niigata University, International
    Id: Kyowakai Medical Research Grant

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