Wang Changyu, Lv Jianjun, Xue Chengxu, Li Jiawen, Liu Yanqing, Xu Danni, Jiang Yuting, Jiang Shuai, Zhu Minghui, Yang Yang, Zhang Shaofei
Department of Cardiology, Xi'an No. 3 Hospital, The Affiliated Hospital of Northwest University, Faculty of Life Sciences and Medicine, Northwest University, Xi'an, China.
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Sciences, Northwest University, Xi'an, China.
Cell Death Discov. 2022 Jul 25;8(1):336. doi: 10.1038/s41420-022-01130-1.
Cytochrome c oxidase subunit VIc (COX6c) is one of the most important subunits of the terminal enzyme of the respiratory chain in mitochondria. Numerous studies have demonstrated that COX6c plays a critical role in the regulation of oxidative phosphorylation (OXPHOS) and energy production. The release of COX6c from the mitochondria may be a hallmark of the intrinsic apoptosis pathway. Moreover, The changes in COX6c expression are widespread in a variety of diseases and can be chosen as a potential biomarker for diagnosis and treatment. In light of its exclusive effects, we present the elaborate roles that COX6c plays in various diseases. In this review, we first introduced basic knowledge regarding COX6c and its functions in the OXPHOS and apoptosis pathways. Subsequently, we described the regulation of COX6c expression and activity in both positive and negative ways. Furthermore, we summarized the elaborate roles that COX6c plays in various diseases, including cardiovascular disease, kidney disease, brain injury, skeletal muscle injury, and tumors. This review highlights recent advances and provides a comprehensive summary of COX6c in the regulation of OXPHOS in multiple diseases and may be helpful for drug design and the prediction, diagnosis, treatment, and prognosis of diseases.
细胞色素c氧化酶亚基VIc（COX6c）是线粒体呼吸链末端酶最重要的亚基之一。大量研究表明，COX6c在氧化磷酸化（OXPHOS）调节和能量产生中起关键作用。COX6c从线粒体释放可能是内源性凋亡途径的一个标志。此外，COX6c表达的变化在多种疾病中广泛存在，可作为诊断和治疗的潜在生物标志物。鉴于其独特作用，我们阐述了COX6c在各种疾病中所起的精细作用。在本综述中，我们首先介绍了关于COX6c及其在OXPHOS和凋亡途径中功能的基础知识。随后，我们描述了COX6c表达和活性的正负调节方式。此外，我们总结了COX6c在各种疾病中所起的精细作用，包括心血管疾病、肾脏疾病、脑损伤、骨骼肌损伤和肿瘤。本综述突出了最新进展，并全面总结了COX6c在多种疾病中对OXPHOS的调节作用，可能有助于药物设计以及疾病的预测、诊断、治疗和预后判断。
