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

Abstract

Assembly of the dimeric complex III (CIII 2 ) in the mitochondrial inner membrane is an intricate process, in which several accessory proteins are involved as assembly factors. Despite numerous studies, this process is yet to be fully understood. Here we report the identification of human OCIAD2 (Ovarian Carcinoma Immunoreactive Antigen domain containing protein 2) protein as an assembly factor for CIII 2 . OCIAD2 was found deregulated in several carcinomas and also in some neurogenerative disorders, however its non-pathological 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 CIII 2 and supercomplex III 2 +IV, and reduction in CIII enzymatic activity. Identification of OCIAD2 as a protein required for assembly of functional CIII 2 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.

Assembly of the dimeric complex III (CIII 2 ) in the mitochondrial inner membrane is an intricate process, in which several accessory proteins are involved as assembly factors. Despite numerous studies, this process is yet to be fully understood. Here we report the identification of human OCIAD2 (Ovarian Carcinoma Immunoreactive Antigen domain containing protein 2) protein as an assembly factor for CIII 2 . OCIAD2 was found deregulated in several carcinomas and also in some neurogenerative disorders, however its non-pathological 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 CIII 2 and supercomplex III 2 +IV, and reduction in CIII enzymatic activity. Identification of OCIAD2 as a protein required for assembly of functional CIII 2 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.