Molecular Regulations of FUNDC1 at ER-Mitochondria Contacts Under Hypoxic Stress

Yi Zhang; Haixia Zhuang; Hao Liu; Du Feng

doi:10.1177/25152564221092487

Molecular Regulations of FUNDC1 at ER-Mitochondria Contacts Under Hypoxic Stress

Contact (Thousand Oaks). 2022 Apr 5:5:25152564221092487. doi: 10.1177/25152564221092487. eCollection 2022 Jan-Dec.

Authors

Yi Zhang^{1

2

3}, Haixia Zhuang¹, Hao Liu⁴, Du Feng^{1

3

4}

Affiliations

¹ Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences; Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
² GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
³ State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China.
⁴ The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou, China.

Abstract

A recent research paper published in Journal of Cell Biology by Chen and colleagues describes a novel mechanism by which the MAM (Mitochondrial-associated endoplasmic reticulum membrane) protein FUNDC1 (FUN14 domain-containing protein 1) regulates mitochondrial division through altered protein post-translational modifications under hypoxic stress. The authors found that in a hypoxic environment, the endoplasmic reticulum-localized deubiquitinating enzyme USP19 accumulates at the MAM and interacts with the enriched mitochondrial outer membrane protein FUNDC1, which subsequently induces its deubiquitination and promotes the oligomerization and activity of DRP1, and mitochondria eventually divide in the presence of DRP1. This article provides new insights into the regulation of mitochondrial dynamics by FUNDC1 under hypoxic condition.

Keywords: DRP1; FUNDC1; MAM; Mitochondria; USP19.