title: CDK5-dependent inhibitory phosphorylation of Drp1 during neuronal maturation.
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.
authors.affiliation: Department of Anatomy, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Bongki
authors.initials: B
authors.lastname: Cho
authors.affiliation: Department of Anatomy, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Hyo Min
authors.initials: HM
authors.lastname: Cho
authors.affiliation: Department of Anatomy, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Life Science, Pohang University of Science and Technology, Pohang, Gyungbuk, Republic of Korea.
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Jeong
authors.affiliation: Department of Life Science, Pohang University of Science and Technology, Pohang, Gyungbuk, Republic of Korea.
authors.forename: Sang Ki
authors.initials: SK
authors.lastname: Park
authors.affiliation: Center for Neural Science and WCI Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, Republic of Korea.
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Hwang
authors.affiliation: 1] Center for Neural Science and WCI Center for Functional Connectomics, Korea Institute of Science and Technology, Seoul, Republic of Korea [2] Department of Physiology, Institute of Health Science, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Anatomy, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Woon Ryoung
authors.initials: WR
authors.lastname: Kim
authors.affiliation: Department of Anatomy, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Anatomy, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D034281:Dynamins / Q000032:analysis / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D008938:Mitosis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats
chemical_list: D051360:Cyclin-Dependent Kinase 5; C519851:Dnm1l protein, rat; D034281:Dynamins