Details

Autor(en) / Beteiligte

• Chen, Guo
• Han, Zhe
• Feng, Du
• Chen, Yanfang
• Chen, Linbo
• Wu, Hao
• Huang, Li
• Zhou, Changqian
• Cai, Xiangyu
• Fu, Changying
• Duan, Liangwei
• Wang, Xiaohui
• Liu, Lei
• Liu, Xinqi
• Shen, Yuequan
• Zhu, Yushan
• Chen, Quan

Titel

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

Ist Teil von

• Molecular cell, 2014-05, Vol.54 (3), p.362-377

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •FUNDC1 dephosphorylation at Ser-13 activates mitophagy•PGAM5 and CK2 regulate the reversible phosphorylation of FUNDC1•Knockdown of PGAM5 abrogates receptor-mediated mitophagy•CK2 and Src kinase functionally cooperate to regulate FUNDC1-mediated mitophagy Mitochondrial autophagy, or mitophagy, is a major mechanism involved in mitochondrial quality control. Chen et al. describe a regulatory signaling loop comprising the PGAM5 phosphatase and CK2 that controls receptor-mediated mitophagy.