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Ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) is a novel complex III-specific assembly factor in mitochondria.

Molecular biology of the cell (2022-01-27)
Katarzyna Justyna Chojnacka, Praveenraj Elancheliyan, Ben Hur Marins Mussulini, Karthik Mohanraj, Sylvie Callegari, Aleksandra Gosk, Tomasz Banach, Tomasz Góral, Karolina Szczepanowska, Peter Rehling, Remigiusz Adam Serwa, Agnieszka Chacinska
ABSTRACT

Assembly of the dimeric complex III (CIII2) in the mitochondrial inner membrane is an intricate process in which several accessory proteins are involved as assembly factors. Despite numerous studies, this process has yet to be fully understood. Here we report the identification of human OCIAD2 (ovarian carcinoma immunoreactive antigen-like protein 2) as an assembly factor for CIII2. OCIAD2 was found to be deregulated in several carcinomas and also in some neurogenerative disorders; however, its nonpathological role had not been elucidated.  We have shown that OCIAD2 localizes to mitochondria and interacts with electron transport chain (ETC) proteins. Complete loss of OCIAD2 using gene editing in HEK293 cells resulted in abnormal mitochondrial morphology, a substantial decrease of both CIII2 and supercomplex III2+IV, and a reduction in CIII enzymatic activity. Identification of OCIAD2 as a protein required for assembly of functional CIII2 provides a new insight into the biogenesis and architecture of the ETC. Elucidating the mechanism of OCIAD2 action is important both for the understanding of cellular metabolism and for an understanding of its role in malignant transformation.

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