USP19 promotes hypoxia-induced mitochondrial division via FUNDC1 at ER-mitochondria contact sites |
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| Authors: | Peiyuan Chai Yiru Cheng Chuyi Hou Lei Yin Donghui Zhang Yingchun Hu Qingzhou Chen Pengli Zheng Junlin Teng Jianguo Chen |
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| Institution: | 1.Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, China;2.State Key Laboratory of Protein and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, China;3.Core Facilities, College of Life Sciences, Peking University, Beijing, China;4.Center for Quantitative Biology, Peking University, Beijing, China |
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| 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. |
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