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卵巢癌免疫反应性抗原样蛋白 2（OCIAD2）是一种新型的线粒体复合体 III 特异性组装因子。

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

机构信息

Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland.

ReMedy International Research Agenda Unit, International Institute of Molecular Mechanisms and Machines (IMol), Polish Academy of Sciences, 00-783 Warsaw, Poland.

出版信息

Mol Biol Cell. 2022 Apr 1;33(4):ar29. doi: 10.1091/mbc.E21-03-0143. Epub 2022 Jan 26.

DOI:10.1091/mbc.E21-03-0143
PMID:35080992
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9250361/
Abstract

Assembly of the dimeric complex III (CIII) 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 CIII. 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 CIII and supercomplex III+IV, and a reduction in CIII enzymatic activity. Identification of OCIAD2 as a protein required for assembly of functional CIII 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

摘要

线粒体膜中二聚体复合物 III（CIII）的组装是一个复杂的过程，其中涉及几种辅助蛋白作为组装因子。尽管进行了大量研究，但这个过程尚未被完全理解。在这里，我们报告了人源 OCIAD2（卵巢癌免疫反应性抗原样蛋白 2）作为 CIII 组装因子的鉴定。OCIAD2 在几种癌中被发现失调，也在一些神经退行性疾病中被发现失调；然而，其非病理作用尚未阐明。我们已经表明，OCIAD2 定位于线粒体并与电子传递链（ETC）蛋白相互作用。使用基因编辑在 HEK293 细胞中完全缺失 OCIAD2 会导致线粒体形态异常，CIII 和超复合体 III+IV 的含量显著降低，以及 CIII 酶活性降低。将 OCIAD2 鉴定为组装功能性 CIII 所需的蛋白质，为 ETC 的生物发生和结构提供了新的见解。阐明 OCIAD2 作用的机制对于理解细胞代谢以及理解其在恶性转化中的作用都很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/27591f6ab8c7/mbc-33-ar29-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/103564b8dfde/mbc-33-ar29-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/548401ff0330/mbc-33-ar29-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/01ba141f8752/mbc-33-ar29-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/97a437d211fe/mbc-33-ar29-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/3e645c258cde/mbc-33-ar29-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/27591f6ab8c7/mbc-33-ar29-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/103564b8dfde/mbc-33-ar29-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/548401ff0330/mbc-33-ar29-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/01ba141f8752/mbc-33-ar29-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/97a437d211fe/mbc-33-ar29-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/3e645c258cde/mbc-33-ar29-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94fd/9250361/27591f6ab8c7/mbc-33-ar29-g006.jpg

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