Kee Teresa R, Espinoza Gonzalez Pamela, Wehinger Jessica L, Bukhari Mohammed Zaheen, Ermekbaeva Aizara, Sista Apoorva, Kotsiviras Peter, Liu Tian, Kang David E, Woo Jung-A A
USF Health Byrd Alzheimer's Center and Research Institute, Tampa, FL, United States.
Department of Molecular Pharmacology and Physiology, USF Health Morsani College of Medicine, Tampa, FL, United States.
Front Aging Neurosci. 2021 Apr 22;13:660843. doi: 10.3389/fnagi.2021.660843. eCollection 2021.
Rare mutations in the mitochondrial protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) are associated with Parkinson's disease (PD) and other Lewy body disorders. CHCHD2 is a bi-organellar mediator of oxidative phosphorylation, playing crucial roles in regulating electron flow in the mitochondrial electron transport chain and acting as a nuclear transcription factor for a cytochrome c oxidase subunit (COX4I2) and itself in response to hypoxic stress. CHCHD2 also regulates cell migration and differentiation, mitochondrial cristae structure, and apoptosis. In this review, we summarize the known disease-associated mutations of CHCHD2 in Asian and Caucasian populations, the physiological functions of CHCHD2, how CHCHD2 mutations contribute to α-synuclein pathology, and current animal models of CHCHD2. Further, we discuss the necessity of continued investigation into the divergent functions of CHCHD2 and CHCHD10 to determine how mutations in these similar mitochondrial proteins contribute to different neurodegenerative diseases.
线粒体蛋白卷曲螺旋-螺旋-卷曲螺旋-螺旋结构域包含蛋白2（CHCHD2）中的罕见突变与帕金森病（PD）及其他路易体疾病相关。CHCHD2是氧化磷酸化的双细胞器介质，在调节线粒体电子传递链中的电子流以及作为细胞色素c氧化酶亚基（COX4I2）和其自身响应缺氧应激的核转录因子方面发挥关键作用。CHCHD2还调节细胞迁移和分化、线粒体嵴结构及细胞凋亡。在本综述中，我们总结了亚洲和白种人群中已知的与疾病相关的CHCHD2突变、CHCHD2的生理功能、CHCHD2突变如何导致α-突触核蛋白病理改变以及当前CHCHD2的动物模型。此外，我们讨论了持续研究CHCHD2和CHCHD10不同功能的必要性，以确定这些相似的线粒体蛋白中的突变如何导致不同的神经退行性疾病。
