Soubannier Vincent, McBride Heidi M
University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada K1Y 4W7.
Biochim Biophys Acta. 2009 Jan;1793(1):154-70. doi: 10.1016/j.bbamcr.2008.07.008. Epub 2008 Jul 23.
Mitochondria evolved from alpha-proteobacteria captured within a host between two and three billion years ago. This origin resulted in the formation of a double-layered organelle resulting in four distinct sub-compartments: the outer membrane, the intermembrane space, the inner membrane and the matrix. The inner membrane is organized in cristae, harboring the respiratory chain and ATP synthase complexes responsible of the oxidative phosphorylation, the main energy-generating system of the cell. It is generally considered that the ultrastructure of the inner membrane provides a large variety of morphologies that facilitate metabolic output. This classical view of mitochondria as bean-shaped organelles was static until in the last decade when new imaging studies and genetic screens provided a more accurate description of a dynamic mitochondrial reticulum that fuse and divide continuously. Since then significant findings have been made in the study of machineries responsible for fusion, fission and motility, however the mechanisms and signals that regulate mitochondrial dynamics are only beginning to emerge. A growing body of evidence indicates that metabolic and cellular signals influence mitochondrial dynamics, leading to a new understanding of how changes in mitochondrial shape can have a profound impact on the functional output of the organelle. The mechanisms that regulate mitochondrial morphology are incompletely understood, but evidence to date suggests that the morphology machinery is modulated through the use of post-translational modifications, including nucleotide-binding proteins, phosphorylation, ubiquitination, SUMOylation, and changes in the lipid environment. This review focuses on the molecular switches that control mitochondrial dynamics and the integration of mitochondrial morphology within cellular signaling cascades.
线粒体起源于20亿至30亿年前被宿主捕获的α-变形菌。这一起源导致了双层细胞器的形成，产生了四个不同的亚区室：外膜、膜间隙、内膜和基质。内膜形成嵴，包含负责氧化磷酸化的呼吸链和ATP合酶复合物，氧化磷酸化是细胞的主要能量产生系统。一般认为内膜的超微结构提供了多种形态，有利于代谢输出。线粒体作为豆形细胞器的这种经典观点一直是静态的，直到过去十年，新的成像研究和基因筛选对动态线粒体网状结构进行了更准确的描述，线粒体网状结构不断融合和分裂。从那时起，在负责融合、分裂和运动的机制研究方面取得了重大发现，然而调节线粒体动态的机制和信号才刚刚开始显现。越来越多的证据表明，代谢和细胞信号影响线粒体动态，这使人们对线粒体形状的变化如何对细胞器的功能输出产生深远影响有了新的认识。调节线粒体形态的机制尚未完全了解，但迄今为止的证据表明，形态机制是通过翻译后修饰来调节的，包括核苷酸结合蛋白、磷酸化、泛素化、SUMO化以及脂质环境的变化。本综述重点关注控制线粒体动态的分子开关以及线粒体形态在细胞信号级联反应中的整合。
