Ko 2021 Biomolecules

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Publications in the MiPMap
Ko HJ, Tsai CY, Chiou SJ, Lai YL, Wang CH, Cheng JT, Chuang TH, Huang CF, Kwan AL, Loh JK, Hong YR (2021) The phosphorylation status of Drp1-Ser637 by PKA in mitochondrial fission modulates mitophagy via PINK1/Parkin to exert multipolar spindles assembly during mitosis. Biomolecules 11:424.

» PMID: 33805672 Open Access

Ko Huey-Jiun, Tsai Cheng-Yu, Chiou Shean-Jaw, Lai Yun-Ling, Wang Chi-Huei, Cheng Jiin-Tsuey, Chuang Tsung-Hsien, Huang Chi-Ying F, Kwan Aij-Lie, Loh Joon-Khim, Hong Yi-Ren (2021) Biomolecules

Abstract: Mitochondrial fission and fusion cycles are integrated with cell cycle progression. Here we first re-visited how mitochondrial ETC inhibition disturbed mitosis progression, resulting in multipolar spindles formation in HeLa cells. Inhibitors of ETC complex I (rotenone, ROT) and complex III (antimycin A, AA) decreased the phosphorylation of Plk1 T210 and Aurora A T288 in the mitotic phase (M-phase), especially ROT, affecting the dynamic phosphorylation status of fission protein dynamin-related protein 1 (Drp1) and the Ser637/Ser616 ratio. We then tested whether specific Drp1 inhibitors, Mdivi-1 or Dynasore, affected the dynamic phosphorylation status of Drp1. Similar to the effects of ROT and AA, our results showed that Mdivi-1 but not Dynasore influenced the dynamic phosphorylation status of Ser637 and Ser616 in Drp1, which converged with mitotic kinases (Cdk1, Plk1, Aurora A) and centrosome-associated proteins to significantly accelerate mitotic defects. Moreover, our data also indicated that evoking mito-Drp1-Ser637 by protein kinase A (PKA) rather than Drp1-Ser616 by Cdk1/Cyclin B resulted in mitochondrial fission via the PINK1/Parkin pathway to promote more efficient mitophagy and simultaneously caused multipolar spindles. Collectively, this study is the first to uncover that mito-Drp1-Ser637 by PKA, but not Drp1-Ser616, drives mitophagy to exert multipolar spindles formation during M-phase. Keywords: Drp1, PKA, Centrosomes, Mitochondria, Mitophagy, Multipolar spindles, Phosphorylation Bioblast editor: Reiswig R


Labels: MiParea: Respiration, mt-Structure;fission;fusion 


Organism: Human  Tissue;cell: HeLa  Preparation: Intact cells  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase 

Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k 

2021-07