RRC ID 74108
Author Furukawa K, Fukuda T, Yamashita SI, Saigusa T, Kurihara Y, Yoshida Y, Kirisako H, Nakatogawa H, Kanki T.
Title The PP2A-like Protein Phosphatase Ppg1 and the Far Complex Cooperatively Counteract CK2-Mediated Phosphorylation of Atg32 to Inhibit Mitophagy.
Journal Cell Rep
Abstract Mitophagy plays an important role in mitochondrial quality control. In yeast, phosphorylation of the mitophagy receptor Atg32 by casein kinase 2 (CK2) upon induction of mitophagy is a prerequisite for interaction of Atg32 with Atg11 (an adaptor protein for selective autophagy) and following delivery of mitochondria to the vacuole for degradation. Because CK2 is constitutively active, Atg32 phosphorylation must be precisely regulated to prevent unrequired mitophagy. We found that the PP2A (protein phosphatase 2A)-like protein phosphatase Ppg1 was essential for dephosphorylation of Atg32 and inhibited mitophagy. We identified the Far complex proteins, Far3, Far7, Far8, Far9, Far10, and Far11, as Ppg1-binding proteins. Deletion of Ppg1 or Far proteins accelerated mitophagy. Deletion of a cytoplasmic region (amino acid residues 151-200) of Atg32 caused the same phenotypes as in ppg1Δ cells, which suggested that dephosphorylation of Atg32 by Ppg1 required this region. Therefore, Ppg1 and the Far complex cooperatively dephosphorylate Atg32 to prevent excessive mitophagy.
Volume 23(12)
Pages 3579-3590
Published 2018-6-19
DOI 10.1016/j.celrep.2018.05.064
PII S2211-1247(18)30828-3
PMID 29925000
MeSH Autophagy-Related Proteins / metabolism Casein Kinase II / metabolism* Cytosol / metabolism Gene Deletion Green Fluorescent Proteins / metabolism Mitochondria / metabolism Mitophagy* Models, Biological Multiprotein Complexes / metabolism* Phosphoprotein Phosphatases / metabolism* Phosphorylation Receptors, Cytoplasmic and Nuclear / metabolism Saccharomyces cerevisiae / metabolism* Saccharomyces cerevisiae Proteins / metabolism*
IF 8.109
Yeast BYP9623