The Phosphorylation Status of Drp1-Ser637 by PKA in Mitochondrial Fission Modulates Mitophagy via PINK1/Parkin to Exert Multipolar Spindles Assembly during Mitosis
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 (antimyci...
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doaj-de924470106742cb94f58204081704e62021-03-14T00:01:30ZengMDPI AGBiomolecules2218-273X2021-03-011142442410.3390/biom11030424The Phosphorylation Status of Drp1-Ser637 by PKA in Mitochondrial Fission Modulates Mitophagy via PINK1/Parkin to Exert Multipolar Spindles Assembly during MitosisHuey-Jiun Ko0Cheng-Yu Tsai1Shean-Jaw Chiou2Yun-Ling Lai3Chi-Huei Wang4Jiin-Tsuey Cheng5Tsung-Hsien Chuang6Chi-Ying F. Huang7Aij-Lie Kwan8Joon-Khim Loh9Yi-Ren Hong10Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, TaiwanPh.D. Program in Environmental and Occupational Medicine, National Health Research Institutes, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, TaiwanDepartment of Biotechnology, Kaohsiung Medical University, Kaohsiung 807378, TaiwanDepartment of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, TaiwanPh.D. Program in Environmental and Occupational Medicine, National Health Research Institutes, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanDepartment of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, TaiwanGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, TaiwanMitochondrial 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.https://www.mdpi.com/2218-273X/11/3/424mitochondriaDrp1PKAphosphorylationmitophagycentrosomes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Huey-Jiun Ko Cheng-Yu Tsai Shean-Jaw Chiou Yun-Ling Lai Chi-Huei Wang Jiin-Tsuey Cheng Tsung-Hsien Chuang Chi-Ying F. Huang Aij-Lie Kwan Joon-Khim Loh Yi-Ren Hong |
spellingShingle |
Huey-Jiun Ko Cheng-Yu Tsai Shean-Jaw Chiou Yun-Ling Lai Chi-Huei Wang Jiin-Tsuey Cheng Tsung-Hsien Chuang Chi-Ying F. Huang Aij-Lie Kwan Joon-Khim Loh Yi-Ren Hong The Phosphorylation Status of Drp1-Ser637 by PKA in Mitochondrial Fission Modulates Mitophagy via PINK1/Parkin to Exert Multipolar Spindles Assembly during Mitosis Biomolecules mitochondria Drp1 PKA phosphorylation mitophagy centrosomes |
author_facet |
Huey-Jiun Ko Cheng-Yu Tsai Shean-Jaw Chiou Yun-Ling Lai Chi-Huei Wang Jiin-Tsuey Cheng Tsung-Hsien Chuang Chi-Ying F. Huang Aij-Lie Kwan Joon-Khim Loh Yi-Ren Hong |
author_sort |
Huey-Jiun Ko |
title |
The Phosphorylation Status of Drp1-Ser637 by PKA in Mitochondrial Fission Modulates Mitophagy via PINK1/Parkin to Exert Multipolar Spindles Assembly during Mitosis |
title_short |
The Phosphorylation Status of Drp1-Ser637 by PKA in Mitochondrial Fission Modulates Mitophagy via PINK1/Parkin to Exert Multipolar Spindles Assembly during Mitosis |
title_full |
The Phosphorylation Status of Drp1-Ser637 by PKA in Mitochondrial Fission Modulates Mitophagy via PINK1/Parkin to Exert Multipolar Spindles Assembly during Mitosis |
title_fullStr |
The Phosphorylation Status of Drp1-Ser637 by PKA in Mitochondrial Fission Modulates Mitophagy via PINK1/Parkin to Exert Multipolar Spindles Assembly during Mitosis |
title_full_unstemmed |
The Phosphorylation Status of Drp1-Ser637 by PKA in Mitochondrial Fission Modulates Mitophagy via PINK1/Parkin to Exert Multipolar Spindles Assembly during Mitosis |
title_sort |
phosphorylation status of drp1-ser637 by pka in mitochondrial fission modulates mitophagy via pink1/parkin to exert multipolar spindles assembly during mitosis |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2021-03-01 |
description |
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. |
topic |
mitochondria Drp1 PKA phosphorylation mitophagy centrosomes |
url |
https://www.mdpi.com/2218-273X/11/3/424 |
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