Mitotic Phosphorylation of Dynamin-related GTPase Drp1 Participates in Mitochondrial Fission*

By Naoko Taguchi, Naotada Ishihara, A. Jofuku, T. Oka, K. Mihara. Journal of Biological Chemistry, 2007

1,207 citations recorded by the source corpus.

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.

Subfields: Clinical Biochemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4c5bc487375bda998fbec2b86dbe4515b99223d8

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In Clinical Biochemistry

1. D. C. Chan
2. R. Youle
3. B. Westermann
4. Hsiuchen Chen
5. D. Seol
6. Seon-Yong Jeong
7. Xiongwei Zhu
8. Xinglong Wang

In Molecular Biology

1. D. C. Chan
2. R. Youle
3. B. Westermann
4. L. Scorrano
5. M. Liesa
6. Hsiuchen Chen
7. W. Ding
8. D. Suen

Citations in the corpus

• Whole cell 3D STORM reveals interactions between cellular structures with nanometer-scale resolution (2008, neutral): “: the interconnected tubular network of mitochondria present during interphase disintegrates during the mitotic phas”
• Mitochondrial fusion and fission in cell life and death (2010, background): “Three protein kinases have been identified that phosphorylate different DRP1 Ser residues: cyclin-dependent kinase 1 (CDK1)–cyclin”
• Reversible phosphorylation of Drp1 by cyclic AMP‐dependent protein kinase and calcineurin regulates mitochondrial fission and cell death (2007, background): “…activity of Drp1 (Harder et al, 2004; Nakamura et al, 2006; Wasiak et al, 2007), and a recent report identified a cyclin-dependent kinase (Cdk) site in Drp1, phosphorylation of which might be responsible for a transient breakdown of the mitochondrial reticulum during mitosis (Taguchi et al, 2007).”
• The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. (2008, background): “Drp1 is activated by cyclin-dependent kinase 1/cyclin B-mediated phosphorylation during mitosis (Taguchi et al., 2007) and inactivated by cAMPdependent protein kinase (PKA) in quiescent cells (Chang and Blackstone, 2007; Cribbs and Strack, 2007).”
• Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission (2013, background): “Drp1 is also phosphorylated at S616, and this modification has been shown to positively regulate Drp1 function during mitosis (Taguchi et al., 2007; Kashatus et al., 2011).”
• Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation (2011, background): “Phosphorylation of Drp1 at S616 by Cdk1/cyclin B results in increased Drp1 fission activity (13).”
• Mitochondrial dynamics and mitochondrial quality control (2014, background): “At the onset of mitosis, Drp1 is phosphorylated by Cdk1/ Cyclin B at Ser585, which increases Drp1 GTPase activity [26].”
• Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control (2014, methodology): “…UUGGCCUAAGAAGAAAUGGA-3′ (Chen et al, 2007)], beclin-1 [1:1 mixture of 5′-CAGUUUGGCACAAUCAAUAACUUCA-3′ and 5′-CAG GAACUCACAGCUCCAUUACUUA-3′ (Hoyer-Hansen et al, 2005)], Drp1 [5′-ACUAUUGAAGGAACUGCAAAAUAUA-3′ (Taguchi et al, 2007)] and Rab9 [5′-AAGUUUGAUACCCAGCUCUUCCAUA-3′ (Ganley et al, 2004)].”
• Erk2 phosphorylation of Drp1 promotes mitochondrial fission and MAPK-driven tumor growth (2015, background): “These processes are regulated by specific protein-protein interactions between Drp1 and mitochondrial membrane proteins, as well as posttranslational modifications, including phosphorylation of S616, which promotes Drp1 activity (Taguchi et al., 2007), and S637, which inhibits its activity (Chang an”
• Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice (2009, background): “At the early mitotic phase in control cells, mitochondria were fragmented and dispersed throughout the cytoplas”
• Impaired Balance of Mitochondria Fission and Fusion in Alzheimer Disease (2009, background): “, 2008), it appears that phosphorylation of DLP1 at Ser 616 activates mitochondrial fission activity (Taguchi et al., 2007).”