Association and dissociation between the mitochondria! Far complex and Atg32 regulate mitophagy
Open Access
- 15 December 2020
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
Abstract
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.Funding Information
- Japan Society for the Promotion of Science (19K22419)
- Japan Society for the Promotion of Science (19H05712)
- Japan Society for the Promotion of Science (18H04858)
- Japan Society for the Promotion of Science (18H04691)
- Japan Society for the Promotion of Science (17H03671)
- Japan Society for the Promotion of Science (18K06129)
- Japan Agency for Medical Research and Development (JP18gm6110013h0001)
- Takeda Science Foundation
- Noda Institute for Scientific Research
- Institute for Fermentation, Osaka
- Niigata University (Kyowakai Medical Research Grant)
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