CDK5-dependent inhibitory phosphorylation of Drp1 during neuronal maturation

Bongki Cho, Hyun Kim, Hyo Min Cho, Hyun Jung Kim, Jaehoon Jeong, Sang Ki Park, Eun Mi Hwang, Jae-Yong Park, Woon Ryoung Kim, Woong Sun

Research output: Contribution to journalArticle

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Abstract

Mitochondrial functions are essential for the survival and function of neurons. Recently, it has been demonstrated that mitochondrial functions are highly associated with mitochondrial morphology, which is dynamically changed by the balance between fusion and fission. Mitochondrial morphology is primarily controlled by the activation of dynamin-related proteins including dynamin-related protein 1 (Drp1), which promotes mitochondrial fission. Drp1 activity is regulated by several post-translational modifications, thereby modifying mitochondrial morphology. Here, we found that phosphorylation of Drp1 at serine 616 (S616) is mediated by cyclin-dependent kinase 5 (CDK5) in post-mitotic rat neurons. Perturbation of CDK5 activity modified the level of Drp1S616 phosphorylation and mitochondrial morphology in neurons. In addition, phosphorylated Drp1S616 preferentially localized as a cytosolic monomer compared with total Drp1. Furthermore, roscovitine, a chemical inhibitor of CDKs, increased oligomerization and mitochondrial translocation of Drp1, suggesting that CDK5-dependent phosphorylation of Drp1 serves to reduce Drp1's fission-promoting activity. Taken together, we propose that CDK5 has a significant role in the regulation of mitochondrial morphology via inhibitory phosphorylation of Drp1S616 in post-mitotic neurons.

Original languageEnglish
Article numbere105
JournalExperimental and Molecular Medicine
Volume46
Issue number7
DOIs
Publication statusPublished - 2014 Jan 1

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Cyclin-Dependent Kinase 5
Dynamins
Phosphorylation
Neurons
Proteins
Mitochondrial Dynamics
Oligomerization
Post Translational Protein Processing
Serine
Rats
Fusion reactions
Monomers
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

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CDK5-dependent inhibitory phosphorylation of Drp1 during neuronal maturation. / Cho, Bongki; Kim, Hyun; Cho, Hyo Min; Kim, Hyun Jung; Jeong, Jaehoon; Park, Sang Ki; Hwang, Eun Mi; Park, Jae-Yong; Kim, Woon Ryoung; Sun, Woong.

In: Experimental and Molecular Medicine, Vol. 46, No. 7, e105, 01.01.2014.

Research output: Contribution to journalArticle

Cho, Bongki ; Kim, Hyun ; Cho, Hyo Min ; Kim, Hyun Jung ; Jeong, Jaehoon ; Park, Sang Ki ; Hwang, Eun Mi ; Park, Jae-Yong ; Kim, Woon Ryoung ; Sun, Woong. / CDK5-dependent inhibitory phosphorylation of Drp1 during neuronal maturation. In: Experimental and Molecular Medicine. 2014 ; Vol. 46, No. 7.
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