Huang Cheng, Deng Kun, Wu Minghua
Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China; NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410008, China.
Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China; NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan 410008, China.
Int J Biol Macromol. 2023 Apr 30;235:123755. doi: 10.1016/j.ijbiomac.2023.123755. Epub 2023 Feb 20.
Mitochondria are centers of energy metabolism. The mitochondrial network is shaped by mitochondrial dynamics, including the processes of mitochondrial fission and fusion and cristae remodeling. The cristae folded by the inner mitochondrial membrane are sites of the mitochondrial oxidative phosphorylation (OXPHOS) system. However, the factors and their coordinated interplay in cristae remodeling and linked human diseases have not been fully demonstrated. In this review, we focus on key regulators of cristae structure, including the mitochondrial contact site and cristae organizing system, optic atrophy-1, mitochondrial calcium uniporter, and ATP synthase, which function in the dynamic remodeling of cristae. We summarized their contribution to sustaining functional cristae structure and abnormal cristae morphology, including a decreased number of cristae, enlarged cristae junctions, and cristae as concentric ring structures. These abnormalities directly impact cellular respiration and are caused by dysfunction or deletion of these regulators in diseases such as Parkinson's disease, Leigh syndrome, and dominant optic atrophy. Identifying the important regulators of cristae morphology and understanding their role in sustaining mitochondrial morphology could be applied to explore the pathologies of diseases and to develop relevant therapeutic tools.
线粒体是能量代谢的中心。线粒体网络由线粒体动力学塑造，包括线粒体分裂、融合以及嵴重塑过程。线粒体内膜折叠形成的嵴是线粒体氧化磷酸化（OXPHOS）系统的场所。然而，嵴重塑过程中的相关因素及其协同作用以及与之相关的人类疾病尚未得到充分阐明。在本综述中，我们聚焦于嵴结构的关键调节因子，包括线粒体接触位点与嵴组织系统、视神经萎缩蛋白1、线粒体钙单向转运体和ATP合酶，它们在嵴的动态重塑中发挥作用。我们总结了它们对维持功能性嵴结构和异常嵴形态的作用，包括嵴数量减少、嵴连接扩大以及嵴呈同心环结构。这些异常直接影响细胞呼吸，并且是由帕金森病、 Leigh综合征和显性视神经萎缩等疾病中这些调节因子的功能障碍或缺失所导致的。确定嵴形态的重要调节因子并了解它们在维持线粒体形态中的作用，可用于探索疾病的病理机制并开发相关治疗工具。
