Ko 2021 Biomolecules
| 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. |
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
