1. Regulation of mitochondrial morphology by APC/CCdh1-mediated control of Drp1 stability
- Author
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Chih-Sheng Yang, Christopher B. Newgard, Wanli Tang, Jonathan L. Coloff, Erika Segear Johnson, Christopher D. Freel, Jie An, Jeffrey C. Rathmell, Judy Qiju Wu, Olga Ilkayeva, Sarah R. Horn, Sally Kornbluth, and Michael J. Thomenius
- Subjects
Dynamins ,Proteasome Endopeptidase Complex ,endocrine system ,Cell division ,Ubiquitin-Protein Ligases ,Gene Expression ,Mitosis ,Biology ,Mitochondrion ,Transfection ,Anaphase-Promoting Complex-Cyclosome ,GTP Phosphohydrolases ,Mitochondrial Proteins ,03 medical and health sciences ,0302 clinical medicine ,Antigens, CD ,Enzyme Stability ,Humans ,Gene Silencing ,RNA, Small Interfering ,Interphase ,Molecular Biology ,Cytokinesis ,030304 developmental biology ,0303 health sciences ,Cell Cycle ,G1 Phase ,Ubiquitination ,Ubiquitin-Protein Ligase Complexes ,Articles ,Cell Biology ,Cadherins ,Mitochondria ,Cell biology ,HEK293 Cells ,Mitotic exit ,DNAJA3 ,Mitochondrial fission ,Microtubule-Associated Proteins ,030217 neurology & neurosurgery ,HeLa Cells - Abstract
Mitochondria form an interconnected network that undergoes dynamin-related protein 1 (Drp1)-dependent fission during mitosis. We demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven through ubiquitylation of Drp1 by the (anaphase- promoting complex/cyclosome and its coactivator Cdh1) APC/CCdh1 complex. Inhibition Drp1 degradation prevents the normal regrowth of mitochondrial networks during G1 phase., Homeostatic maintenance of cellular mitochondria requires a dynamic balance between fission and fusion, and controlled changes in morphology are important for processes such as apoptosis and cellular division. Interphase mitochondria have been described as an interconnected network that fragments as cells enter mitosis, and this mitotic mitochondrial fragmentation is known to be regulated by the dynamin-related GTPase Drp1 (dynamin-related protein 1), a key component of the mitochondrial division machinery. Loss of Drp1 function and the subsequent failure of mitochondrial division during mitosis lead to incomplete cytokinesis and the unequal distribution of mitochondria into daughter cells. During mitotic exit and interphase, the mitochondrial network reforms. Here we demonstrate that changes in mitochondrial dynamics as cells exit mitosis are driven in part through ubiquitylation of Drp1, catalyzed by the APC/CCdh1 (anaphase-promoting complex/cyclosome and its coactivator Cdh1) E3 ubiquitin ligase complex. Importantly, inhibition of Cdh1-mediated Drp1 ubiquitylation and proteasomal degradation during interphase prevents the normal G1 phase regrowth of mitochondrial networks following cell division.
- Published
- 2011