CAS Center for Excellence in Molecular Cell Sciences, Ministry of Education Key Laboratory for Membrane-less Organelles & Cellular Dynamics, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
FEBS J. 2022 Jan;289(1):262-278. doi: 10.1111/febs.16138. Epub 2021 Aug 3.
Mitochondria form a branched tubular network in many types of cells, depending on a balance between mitochondrial fusion and fission. How mitochondrial fusion and fission are involved in regulating mitochondrial function and cell proliferation is not well understood. Here, we dissected the roles of mitochondrial fusion and fission in mitochondrial function and cell proliferation in fission yeast. We examined mitochondrial membrane potential by staining cells with DiOC and assessed mitochondrial respiration by directly measuring oxygen consumption of cells with a dissolved oxygen respirometer. We found that defects in mitochondrial fission or fusion reduce mitochondrial membrane potential and compromise mitochondrial respiration while the absence of both mitochondrial fusion and fission restores wild type-like respiration, normal membrane potential, and tubular networks of mitochondria. Moreover, we found that the absence of either mitochondrial fission or fusion prolongs the cell cycle and that the absence of both mitochondrial fusion and fission significantly delays cell cycle progression after nitrogen replenishment. The prolonged/delayed cell cycle is likely due to the deregulation of Cdc2 activation. Hence, our work not only establishes an intimate link between mitochondrial morphology and function but also underscores the importance of mitochondrial dynamics in regulating the cell cycle.
线粒体在许多类型的细胞中形成分支管状网络,这取决于线粒体融合和裂变之间的平衡。线粒体融合和裂变如何参与调节线粒体功能和细胞增殖还不太清楚。在这里,我们在裂变酵母中解析了线粒体融合和裂变在线粒体功能和细胞增殖中的作用。我们通过用 DiOC 染色细胞来检测线粒体膜电位,并通过用溶解氧呼吸计直接测量细胞的耗氧量来评估线粒体呼吸作用。我们发现,线粒体裂变或融合的缺陷会降低线粒体膜电位并损害线粒体呼吸作用,而线粒体融合和裂变的缺失则会恢复野生型样呼吸作用、正常的膜电位和线粒体的管状网络。此外,我们发现线粒体裂变或融合的缺失会延长细胞周期,而线粒体融合和裂变的缺失会显著延迟氮源补充后细胞周期的进程。细胞周期的延长/延迟可能是由于 Cdc2 激活的失调所致。因此,我们的工作不仅建立了线粒体形态和功能之间的紧密联系,还强调了线粒体动力学在调节细胞周期中的重要性。