title: CaM kinase I alpha-induced phosphorylation of Drp1 regulates mitochondrial morphology.
abstract: Mitochondria are dynamic organelles that frequently move, divide, and fuse with one another to maintain their architecture and functions. However, the signaling mechanisms involved in these processes are still not well characterized. In this study, we analyze mitochondrial dynamics and morphology in neurons. Using time-lapse imaging, we find that Ca2+ influx through voltage-dependent Ca2+ channels (VDCCs) causes a rapid halt in mitochondrial movement and induces mitochondrial fission. VDCC-associated Ca2+ signaling stimulates phosphorylation of dynamin-related protein 1 (Drp1) at serine 600 via activation of Ca2+/calmodulin-dependent protein kinase Ialpha (CaMKIalpha). In neurons and HeLa cells, phosphorylation of Drp1 at serine 600 is associated with an increase in Drp1 translocation to mitochondria, whereas in vitro, phosphorylation of Drp1 results in an increase in its affinity for Fis1. CaMKIalpha is a widely expressed protein kinase, suggesting that Ca2+ is likely to be functionally important in the control of mitochondrial dynamics through regulation of Drp1 phosphorylation in neurons and other cell types.
authors.affiliation: Department of Physiology and 2Department of Neuroscience, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Han
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Lu
authors.forename: Shun-Ai
authors.initials: SA
authors.lastname: Li
authors.forename: Taku
authors.initials: T
authors.lastname: Kaitsuka
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Tomizawa
authors.forename: Angus C
authors.initials: AC
authors.lastname: Nairn
authors.forename: Kohji
authors.initials: K
authors.lastname: Takei
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsui
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsushita
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1 / Q000378:metabolism*; D034281:Dynamins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine / Q000378:metabolism
chemical_list: D015220:Calcium Channels; C476525:FIS1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011994:Recombinant Proteins; D012694:Serine; D054729:Calcium-Calmodulin-Dependent Protein Kinase Type 1; D034281:Dynamins; D011188:Potassium