A Regulatory Signaling Loop Comprising the PGAM5 Phosphatase and CK2 Controls Receptor-Mediated Mitophagy

被引：687

作者：

Chen, Guo ^{[1
]}

Han, Zhe ^{[1
]}

Feng, Du ^{[1
,2
]}

Chen, Yanfang ^{[1
]}

Chen, Linbo ^{[1
]}

Wu, Hao ^{[3
]}

Huang, Li ^{[3
]}

Zhou, Changqian ^{[1
]}

Cai, Xiangyu ^{[1
]}

Fu, Changying ^{[1
]}

Duan, Liangwei ^{[1
]}

Wang, Xiaohui ^{[3
]}

Liu, Lei ^{[3
]}

Liu, Xinqi ^{[1
]}

Shen, Yuequan ^{[1
]}

Zhu, Yushan ^{[1
]}

Chen, Quan ^{[1
,3
]}

机构：

[1] Nankai Univ, Coll Life Sci, Tianjin Key Lab Prot Sci, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China

[2] Guangdong Med Coll, Inst Neurol, Key Lab Age Associated Cardiac Cerebral Vasc Dis, Zhanjiang 524001, Guangdong, Peoples R China

[3] Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China

来源：

MOLECULAR CELL | 2014年 / 54卷 / 03期

关键词：

PROTEIN-KINASE CK2; MITOCHONDRIAL AUTOPHAGY; PHOSPHORYLATION; PARKIN; ATG32; LC3; TRANSLOCATION; SUBSTRATE; PROMOTES; FISSION;

D O I：

10.1016/j.molcel.2014.02.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Mitochondrial autophagy, or mitophagy, is a major mechanism involved in mitochondrial quality control via selectively removing damaged or unwanted mitochondria. Interactions between LC3 and mitophagy receptors such as FUNDC1, which harbors an LC3-interacting region (LIR), are essential for this selective process. However, how mitochondrial stresses are sensed to activate receptor-mediated mitophagy remains poorly defined. Here, we identify that the mitochondrially localized PGAM5 phosphatase interacts with and dephosphorylates FUNDC1 at serine 13 (Ser-13) upon hypoxia or carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) treatment. Dephosphorylation of FUNDC1 catalyzed by PGAM5 enhances its interaction with LC3, which is abrogated following knockdown of PGAM5 or the introduction of a cell-permeable unphosphorylated peptide encompassing the Ser-13 and LIR of FUNDC1. We further observed that CK2 phosphorylates FUNDC1 to reverse the effect of PGAM5 in mitophagy activation. Our results reveal a mechanistic signaling pathway linking mitochondria-damaging signals to the dephosphorylation of FUNDC1 by PGAM5, which ultimately induces mitophagy.

引用

页码：362 / 377

页数：16

共 56 条

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Phosphorylation of Serine 114 on Atg32 mediates mitophagy [J].