Daumke Oliver, van der Laan Martin
Structural Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
Nat Rev Mol Cell Biol. 2025 May 14. doi: 10.1038/s41580-025-00854-z.
Mitochondria display intricately shaped deep invaginations of the mitochondrial inner membrane (MIM) termed cristae. This peculiar membrane architecture is essential for diverse mitochondrial functions, such as oxidative phosphorylation or the biosynthesis of cellular building blocks. Conserved protein nano-machineries such as FF-ATP synthase oligomers and the mitochondrial contact site and cristae organizing system (MICOS) act as adaptable protein-lipid scaffolds controlling MIM biogenesis and its dynamic remodelling. Signal-dependent rearrangements of cristae architecture and MIM fusion events are governed by the dynamin-like GTPase optic atrophy 1 (OPA1). Recent groundbreaking structural insights into these nano-machineries have considerably advanced our understanding of the functional architecture of mitochondria. In this Review, we discuss how the MIM-shaping machineries cooperate to control cristae and crista junction dynamics, including MIM fusion, in response to cellular signalling pathways. We also explore how mutations affecting MIM-shaping machineries compromise mitochondrial functions.
线粒体的线粒体内膜（MIM）呈现出复杂形状的深深内陷，称为嵴。这种独特的膜结构对于多种线粒体功能至关重要，例如氧化磷酸化或细胞构件的生物合成。诸如FF-ATP合酶寡聚体和线粒体接触位点及嵴组织系统（MICOS）等保守的蛋白质纳米机器，作为适应性蛋白质-脂质支架，控制着线粒体内膜的生物发生及其动态重塑。嵴结构的信号依赖性重排和线粒体内膜融合事件由动力蛋白样GTP酶视神经萎缩蛋白1（OPA1）调控。最近对这些纳米机器的开创性结构见解极大地推进了我们对线粒体功能结构的理解。在本综述中，我们讨论了线粒体内膜塑形机器如何协同作用，以响应细胞信号通路控制嵴和嵴连接动力学，包括线粒体内膜融合。我们还探讨了影响线粒体内膜塑形机器的突变如何损害线粒体功能。
