Human OCIAD2 binding partners and the effect of OCIAD2 depletion on mitochondrial protein levels

ABSTRACT: Assembly of the oxidative phoshorylation dimeric complex III (CIII2) in the mitochondrial inner membrane is an intricate process in which many factors are involved. Despite many studies this process is yet to be completely understood. Here we report the identification of human OCIAD2 (Ovarian Carcinoma Immunoreactive Antigen domain containing protein 2) as an assembly factor for CIII2. OCIAD2 was found deregulated in several carcinomas and in some neurodegenerative disorders; however its non-pathological role was not elucidated to date. 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, decrease assembly of both CIII2 and supercomplex III2+IV and decreased activities of complex I and III. 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 understanding of its role in the malignant transformation. This work includes two proteomic datasets that were acquired and analyzed to aid: 1) the identification of protein binding partners of OCIAD2 via co-immunoprecipitation; 2) the quantification of changes induced to protein levels in isolated mitochondria upon deletion of OCIAD2 in cells.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Remigiusz Serwa  

LAB HEAD: Agnieszka Chacinska

PROVIDER: PXD023025 | Pride | 2022-08-12

REPOSITORIES: Pride