Open AccessUSP19 promotes hypoxia-induced mitochondrial division via FUNDC1 at ER-mitochondria contact sites
Author(s) -
Peiyuan Chai,
Yunjie Cheng,
Chuyi Hou,
Lei Yin,
Donghui Zhang,
Yingchun Hu,
Qingzhou Chen,
Pengli Zheng,
Teng Jiang,
Jianguo Chen
Publication year - 2021
Publication title -
the journal of cell biology/the journal of cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.414
H-Index - 380
eISSN - 1540-8140
pISSN - 0021-9525
DOI - 10.1083/jcb.202010006
Subject(s) - mitochondrion , mitochondrial fission , microbiology and biotechnology , hypoxia (environmental) , cytosol , biology , chemistry , biochemistry , oxygen , enzyme , organic chemistry
The ER tethers tightly to mitochondria and the mitochondrial protein FUNDC1 recruits Drp1 to ER-mitochondria contact sites, subsequently facilitating mitochondrial fission and preventing mitochondria from undergoing hypoxic stress. However, the mechanisms by which the ER modulates hypoxia-induced mitochondrial fission are poorly understood. Here, we show that USP19, an ER-resident deubiquitinase, accumulates at ER-mitochondria contact sites under hypoxia and promotes hypoxia-induced mitochondrial division. In response to hypoxia, USP19 binds to and deubiquitinates FUNDC1 at ER-mitochondria contact sites, which facilitates Drp1 oligomerization and Drp1 GTP-binding and hydrolysis activities, thereby promoting mitochondrial division. Our findings reveal a unique hypoxia response pathway mediated by an ER protein that regulates mitochondrial dynamics.