Department of Cellular Biochemistry, University Medical Center Göttingen, Germany.
Göttinger Zentrum für Molekulare Biowissenschaften - GZMB, Göttingen, Germany.
FEBS Lett. 2021 Apr;595(8):1159-1183. doi: 10.1002/1873-3468.14089.
Mitochondria play a key role in cellular signalling, metabolism and energetics. Proper architecture and remodelling of the inner mitochondrial membrane are essential for efficient respiration, apoptosis and quality control in the cell. Several protein complexes including mitochondrial contact site and cristae organizing system (MICOS), F F -ATP synthase, and Optic Atrophy 1 (OPA1), facilitate formation, maintenance and stability of cristae membranes. MICOS, the F F -ATP synthase, OPA1 and inner membrane phospholipids such as cardiolipin and phosphatidylethanolamine interact with each other to organize the inner membrane ultra-structure and remodel cristae in response to the cell's demands. Functional alterations in these proteins or in the biosynthesis pathway of cardiolipin and phosphatidylethanolamine result in an aberrant inner membrane architecture and impair mitochondrial function. Mitochondrial dysfunction and abnormalities hallmark several human conditions and diseases including neurodegeneration, cardiomyopathies and diabetes mellitus. Yet, they have long been regarded as secondary pathological effects. This review discusses emerging evidence of a direct relationship between protein- and lipid-dependent regulation of the inner mitochondrial membrane morphology and diseases such as fatal encephalopathy, Leigh syndrome, Parkinson's disease, and cancer.
线粒体在细胞信号转导、代谢和能量学中发挥着关键作用。适当的内膜结构和重塑对于细胞中有效的呼吸作用、细胞凋亡和质量控制至关重要。几种蛋白复合物，包括线粒体接触位点和嵴组织系统（MICOS）、F F -ATP 合酶和视神经萎缩 1 型（OPA1），有助于嵴膜的形成、维持和稳定性。MICOS、F F -ATP 合酶、OPA1 和内膜磷脂，如心磷脂和磷脂酰乙醇胺，相互作用以组织内膜超结构并响应细胞需求重塑嵴。这些蛋白或心磷脂和磷脂酰乙醇胺生物合成途径中的功能改变导致内膜结构异常，并损害线粒体功能。线粒体功能障碍和异常是几种人类疾病的标志，包括神经退行性疾病、心肌病和糖尿病。然而，它们长期以来一直被视为次要的病理效应。这篇综述讨论了内在线粒体膜形态与疾病之间的直接关系的新证据，如致命性脑病、 Leigh 综合征、帕金森病和癌症。
