USP19 promotes hypoxia-induced mitochondrial division via FUNDC1 at ER-mitochondria contact sites.
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.
Mesh Terms:
Dynamins, Endopeptidases, Endoplasmic Reticulum, Humans, Hypoxia, Membrane Proteins, Mitochondria, Mitochondrial Dynamics, Mitochondrial Proteins, Mitophagy, Phosphorylation, Signal Transduction
Dynamins, Endopeptidases, Endoplasmic Reticulum, Humans, Hypoxia, Membrane Proteins, Mitochondria, Mitochondrial Dynamics, Mitochondrial Proteins, Mitophagy, Phosphorylation, Signal Transduction
J Cell Biol
Date: Dec. 05, 2020
PubMed ID: 33978709
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