Cited by 1,226Mitochondrial Function and PathologyAutophagy in Disease and TherapyCell death mechanisms and regulation

Mitotic phosphorylation of dynamin-related GTPase Drp1 participates in mitochondrial fission.

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Taguchi, Naoko, Ishihara, Naotada, Jofuku, Akihiro, Oka, Toshihiko, Mihara, Katsuyoshi·2007·Journal of Biological Chemistry

Abstract

Organelles are inherited to daughter cells beyond dynamic changes of the membrane structure during mitosis. Mitochondria are dynamic entities, frequently dividing and fusing with each other, during which dynamin-related GTPase Drp1 is required for the fission reaction. In this study, we analyzed mitochondrial dynamics in mitotic mammalian cells. Although mitochondria in interphase HeLa cells are long tubular network structures, they are fragmented in early mitotic phase, and the filamentous network structures are subsequently reformed in the daughter cells. In marked contrast, tubular mitochondrial structures are maintained during mitosis in Drp1 knockdown cells, indicating that the mitochondrial fragmentation in mitosis requires mitochondrial fission by Drp1. Drp1 was specifically phosphorylated in mitosis by Cdk1/cyclin B on Ser-585. Exogenous expression of unphosphorylated mutant Drp1S585A led to reduced mitotic mitochondrial fragmentation. These results suggest that phosphorylation of Drp1 on Ser-585 promotes mitochondrial fission in mitotic cells.

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  • Phosphorylation of DRP1 at serine 616 activates DRP1-mediated mitochondrial fission and its localization on the outer membrane.

    “It is well established that phosphorylation of DRP1 at the serine 616 (S616) site activates DRP1-mediated mitochondrial fission and its localization on the outer membrane (Taguchi et al., 2007; Bo et al., 2018).”

    From Aging promotes an increase in mitochondrial fragmentation in astrocytes (2024) · cites this paper as Taguchi et al., 2007

    The section on mitochondrial fragmentation reports that phosphorylation at rat Drp1 Ser-585 stimulates mitochondrial fission in mitotic cells. It identifies the corresponding site as Ser-590 in human Drp1 isoform 2, not Ser-616, and does not show that phosphorylation promotes Drp1 localization on the outer mitochondrial membrane. The Discussion says the mechanism by which phosphorylation stimulates fission remains unknown. (LLM, conf=0.88)

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Authors
Taguchi, N., Ishihara, N., Jofuku, A., Oka, T., & Mihara, K.
Affiliations
Kyushu University (JP)
Corresponding author
Mihara, Katsuyoshi
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2007-04
Volume
282
Issue
15
Pages
11521-11529
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2138760860
Cited by
1,226
References
5
Citations by year
2026: 55 · 2025: 60 · 2024: 62 · 2023: 78 · 2022: 74 · 2021: 113 · 2020: 103 · 2019: 47 · 2018: 80 · 2017: 76 · 2016: 66 · 2015: 64 · 2014: 60 · 2013: 56 · 2012: 60
FWCI
15.42
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Kanazawa University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
Drp1, dynamin-related GTPase, mitochondrial fission, mitosis, phosphorylation, CDK1/cyclin B, mitochondrial dynamics, mitochondrial fragmentation, HeLa cells, organelle inheritance
MeSH terms
Amino Acid Sequence, Animals, HeLa Cells, Humans, Microtubule-Associated Proteins, Mitochondria, Mitosis, Molecular Sequence Data, Phosphorylation, Phosphoserine, CDC2 Protein Kinase, Cyclin B, GTP Phosphohydrolases, Mitochondrial Proteins, Dynamins, Rats

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