From the, Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
J Intern Med. 2020 Jun;287(6):645-664. doi: 10.1111/joim.13031. Epub 2020 Feb 26.
Mitochondria play central roles in cellular energetics, metabolism and signalling. Efficient respiration, mitochondrial quality control, apoptosis and inheritance of mitochondrial DNA depend on the proper architecture of the mitochondrial membranes and a dynamic remodelling of inner membrane cristae. Defects in mitochondrial architecture can result in severe human diseases affecting predominantly the nervous system and the heart. Inner membrane morphology is generated and maintained in particular by the mitochondrial contact site and cristae organizing system (MICOS), the F F -ATP synthase, the fusion protein OPA1/Mgm1 and the nonbilayer-forming phospholipids cardiolipin and phosphatidylethanolamine. These protein complexes and phospholipids are embedded in a network of functional interactions. They communicate with each other and additional factors, enabling them to balance different aspects of cristae biogenesis and to dynamically remodel the inner mitochondrial membrane. Genetic alterations disturbing these membrane-shaping factors can lead to human pathologies including fatal encephalopathy, dominant optic atrophy, Leigh syndrome, Parkinson's disease and Barth syndrome.
线粒体在细胞能量学、代谢和信号转导中发挥着核心作用。有效的呼吸作用、线粒体质量控制、细胞凋亡以及线粒体 DNA 的遗传依赖于线粒体膜的适当结构和内膜嵴的动态重塑。线粒体结构的缺陷会导致严重的人类疾病，主要影响神经系统和心脏。内膜形态的形成和维持主要是通过线粒体接触位点和嵴组织系统 (MICOS)、F F -ATP 合酶、融合蛋白 OPA1/Mgm1 和非双层形成的磷脂心磷脂和磷脂酰乙醇胺。这些蛋白复合物和磷脂嵌入在一个功能相互作用的网络中。它们相互交流并与其他因素交流，使它们能够平衡嵴生物发生的不同方面，并动态重塑线粒体的内膜。干扰这些膜成形因子的遗传改变可导致人类疾病，包括致命性脑病、显性视神经萎缩、 Leigh 综合征、帕金森病和 Barth 综合征。
