Elucidation of the regulatory mechanism of mitophagy via stress-activated protein kinase and artificial regulation of mitophagy

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K18514
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Niigata University
• Principal Investigator: Furukawa Kentaro 新潟大学, 医歯学総合研究科, 特任助教 (20754493)
• Co-Investigator(Renkei-kenkyūsha): KANKI Tomotake 新潟大学, 大学院医歯学総合研究科, 教授 (50398088)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: ミトコンドリア / オートファジー / マイトファジー / 酵母

Outline of Final Research Achievements

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 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-like protein phosphatase Ppg1 was essential for dephosphorylation of Atg32 and thus inhibited mitophagy. We identified the Far complex consisting of Far3-7-8-9-10-11 proteins as Ppg1-binding proteins. Deletion of Ppg1 or Far proteins accelerated mitophagy. Deletion of a cytoplasmic region (A.A. residues 151-200) of Atg32 caused the same phenotypes as 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.

Free Research Field

細胞生物学