Genome-wide CRISPRi screening identifies OCIAD1 as a prohibitin client and regulatory determinant of mitochondrial Complex III assembly in human cells
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elife-67624-v1.pdf
Description
Published version
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3.14 MB
Format
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Checksum (MD5)
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Author(s)
Le Vasseur, Maxence
Friedman, Jonathan
Jost, Marco
Xu, Jiawei
Yamada, Justin
Kampmann, Martin
Horlbeck, Max A
Salemi, Michelle R
Phinney, Brett S
Weissman, Jonathan S
Date Issued
2021
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Version
Final published version
Abstract
Dysfunction of the mitochondrial electron transport chain (mETC) is a major cause of human mitochondrial diseases. To identify determinants of mETC function, we screened a genome-wide human CRISPRi library under oxidative metabolic conditions with selective inhibition of mitochondrial Complex III and identified ovarian carcinoma immunoreactive antigen (OCIA) domain-containing protein 1 (OCIAD1) as a Complex III assembly factor. We find that OCIAD1 is an inner mitochondrial membrane protein that forms a complex with supramolecular prohibitin assemblies. Our data indicate that OCIAD1 is required for maintenance of normal steady-state levels of Complex III and the proteolytic processing of the catalytic subunit cytochrome c1 (CYC1). In OCIAD1 depleted mitochondria, unprocessed CYC1 is hemylated and incorporated into Complex III. We propose that OCIAD1 acts as an adaptor within prohibitin assemblies to stabilize and/or chaperone CYC1 and to facilitate its proteolytic processing by the IMMP2L protease.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.7554/elife.67624
