Mitra Kasturi, Wunder Christian, Roysam Badrinath, Lin Gang, Lippincott-Schwartz Jennifer
Cell Biology and Metabolism Branch, National Institutes of Health, Building 18T, Room 101, 18 Library Drive, Bethesda, MD 20892-5430, USA.
Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):11960-5. doi: 10.1073/pnas.0904875106. Epub 2009 Jul 15.
Mitochondria undergo fission-fusion events that render these organelles highly dynamic in cells. We report a relationship between mitochondrial form and cell cycle control at the G(1)-S boundary. Mitochondria convert from isolated, fragmented elements into a hyperfused, giant network at G(1)-S transition. The network is electrically continuous and has greater ATP output than mitochondria at any other cell cycle stage. Depolarizing mitochondria at early G(1) to prevent these changes causes cell cycle progression into S phase to be blocked. Inducing mitochondrial hyperfusion by acute inhibition of dynamin-related protein-1 (DRP1) causes quiescent cells maintained without growth factors to begin replicating their DNA and coincides with buildup of cyclin E, the cyclin responsible for G(1)-to-S phase progression. Prolonged or untimely formation of hyperfused mitochondria, through chronic inhibition of DRP1, causes defects in mitotic chromosome alignment and S-phase entry characteristic of cyclin E overexpression. These findings suggest a hyperfused mitochondrial system with specialized properties at G(1)-S is linked to cyclin E buildup for regulation of G(1)-to-S progression.
线粒体经历裂变-融合事件，使这些细胞器在细胞中具有高度动态性。我们报道了线粒体形态与细胞周期在G(1)-S边界处控制之间的关系。线粒体在G(1)-S转变时从孤立的、碎片化的元件转变为高度融合的巨大网络。该网络是电连续的，并且在任何其他细胞周期阶段都比线粒体具有更高的ATP输出。在G(1)早期使线粒体去极化以阻止这些变化会导致细胞周期进入S期受阻。通过急性抑制动力蛋白相关蛋白1（DRP1）诱导线粒体高度融合会使缺乏生长因子而维持静止的细胞开始复制其DNA，并且与细胞周期蛋白E的积累同时发生，细胞周期蛋白E负责G(1)期到S期的进程。通过长期抑制DRP1导致线粒体过度融合的延长或过早形成，会导致有丝分裂染色体排列缺陷和细胞周期蛋白E过表达特征的S期进入缺陷。这些发现表明，在G(1)-S期具有特殊性质的高度融合线粒体系统与细胞周期蛋白E的积累相关联，以调节G(1)期到S期的进程。
