FUNDC1 Regulates Mitochondrial Dynamics at the ER-mitochondrial Contact Site Under Hypoxic conditions

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2016 May 6

PMID 27145933

Citations 180

Authors

Wenxian Wu

Chunxia Lin

Keng Wu

Lei Jiang

Xiaojing Wang

Wen Li

Haixia Zhuang

Xingliang Zhang

Hao Chen

Shupeng Li

Yue Yang

Yue Lu

Jingjing Wang

Runzhi Zhu

Liangqing Zhang

SenFang Sui

Ning Tan

Bin Zhao

Jingjing Zhang

Longxuan Li

Du Feng

Affiliations

Soon will be listed here.

Abstract

In hypoxic cells, dysfunctional mitochondria are selectively removed by a specialized autophagic process called mitophagy. The ER-mitochondrial contact site (MAM) is essential for fission of mitochondria prior to engulfment, and the outer mitochondrial membrane protein FUNDC1 interacts with LC3 to recruit autophagosomes, but the mechanisms integrating these processes are poorly understood. Here, we describe a new pathway mediating mitochondrial fission and subsequent mitophagy under hypoxic conditions. FUNDC1 accumulates at the MAM by associating with the ER membrane protein calnexin. As mitophagy proceeds, FUNDC1/calnexin association attenuates and the exposed cytosolic loop of FUNDC1 interacts with DRP1 instead. DRP1 is thereby recruited to the MAM, and mitochondrial fission then occurs. Knockdown of FUNDC1, DRP1, or calnexin prevents fission and mitophagy under hypoxic conditions. Thus, FUNDC1 integrates mitochondrial fission and mitophagy at the interface of the MAM by working in concert with DRP1 and calnexin under hypoxic conditions in mammalian cells.

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