The BCL2L1 and PGAM5 Axis Defines Hypoxia-induced Receptor-mediated Mitophagy

Overview

Journal Autophagy

Specialty Cell Biology

Date 2014 Aug 16

PMID 25126723

Citations 86

Authors

Hao Wu

Danfeng Xue

Guo Chen

Zhe Han

Li Huang

Chongzhuo Zhu

Xiaohui Wang

Haijing Jin

Jun Wang

Yushan Zhu

Lei Liu

Quan Chen

Affiliations

Soon will be listed here.

Abstract

Receptor-mediated mitophagy is one of the major mechanisms of mitochondrial quality control essential for cell survival. We previously have identified FUNDC1 as a mitophagy receptor for selectively removing damaged mitochondria in mammalian systems. A critical unanswered question is how receptor-mediated mitophagy is regulated in response to cellular and environmental cues. Here, we report the striking finding that BCL2L1/Bcl-xL, but not BCL2, suppresses mitophagy mediated by FUNDC1 through its BH3 domain. Mechanistically, we demonstrate that BCL2L1, but not BCL2, interacts with and inhibits PGAM5, a mitochondrially localized phosphatase, to prevent the dephosphorylation of FUNDC1 at serine 13 (Ser13), which activates hypoxia-induced mitophagy. Our results showed that the BCL2L1-PGAM5-FUNDC1 axis is critical for receptor-mediated mitophagy in response to hypoxia and that BCL2L1 possesses unique functions distinct from BCL2.

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