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USP19 promotes hypoxia-induced mitochondrial division via FUNDC1 at ER-mitochondria contact sites.

ABSTRACT: 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.

SUBMITTER: Chai P

PROVIDER: S-EPMC8127008 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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USP19 promotes hypoxia-induced mitochondrial division via FUNDC1 at ER-mitochondria contact sites.

Chai Peiyuan P Cheng Yiru Y Hou Chuyi C Yin Lei L Zhang Donghui D Hu Yingchun Y Chen Qingzhou Q Zheng Pengli P Teng Junlin J Chen Jianguo J

The Journal of cell biology 20210512 7

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 mitochondria ...[more]

PMID: 33978709

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