RT Journal Article
SR Electronic
T1 Genome-wide CRISPRi screening identifies OCIAD1 as a prohibitin client and regulatory determinant of mitochondrial Complex III assembly in human cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.16.431450
DO 10.1101/2021.02.16.431450
A1 Maxence Le Vasseur
A1 Jonathan R. Friedman
A1 Marco Jost
A1 Jiawei Xu
A1 Justin Yamada
A1 Martin Kampmann
A1 Max A. Horlbeck
A1 Michelle R. Salemi
A1 Brett S. Phinney
A1 Jonathan S. Weissman
A1 Jodi Nunnari
YR 2021
UL http://biorxiv.org/content/early/2021/02/17/2021.02.16.431450.abstract
AB 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 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.Competing Interest StatementJSW consults for and holds equity in KSQ Therapeutics, Maze Therapeutics, and Tenaya Therapeutics. JSW is a venture partner at 5AM Ventures and a member of the Amgen Scientific Advisory Board. MJ consults for Maze Therapeutics.