Cell Cycle-Dependent Mitochondrial Fragmentation Is Required for Proper Mitotic Entry
Lee, Seungmin; Park, Yong-Yea; Kim, Song-Hee; Yoo, Young-Suk; Sun, Xuejun; Chan, Gordon; Cho, Hyeseong
Department of Biochemistry & Molecular Biology
During cell division, mechanisms on partitioning of cellular organelles remain largely unknown. In interphase, a highly interconnected tubular network of mitochondria is observed but it no longer exists in mitotic cells, showing rather fragmented mitochondria. Here, we addressed whether mitochondrial fragmentation is necessary for proper cell cycle progression. Since mitochondrial fission and fusion determine the mitochondrial morphology, we suppressed the mitochondrial fission activity by depleting one of the fission modulator, hFis1. Notably, cells lacking hFis1 showed significantly elongated mitochondria and prevented cell cycle progression into mitotic phase. Few cells entered mitosis under time-lapse microscopy and mitotic accumulation of hFis1 RNAi cells was very limited by aceto-orcein staining. In these cells, cyclin B1 failed to accumulate and the phosphorylated form of histone H3 was not detected, indicating that mitochondrial fragmentation is indispensible for proper mitotic entry. When mitochondrial fragmentation is induced by double knockdown of hFis1 and Opa1, a regulator of mitochondrial fusion, the cells regained ability to enter mitosis. Moreover, beside of low cyclin B1, expressions of cyclin A, cyclin-dependent kinase 1 (Cdk1), polo-like kinase 1 (Plk-1) and aurora B kinase are significantly low in hFis1-depleted cells. Interestingly, introduction of active Plk1 or FoxM1, but not of active cyclin B1/Cdk1, into hFis1 RNAi cells significantly restored the mitotic entry. Together, one of the key functions of mitochondrial fission would be mitochondrial reorganization at G2 phase that is essential for proper mitotic entry.
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