title: Mitochondrial fission protein Drp1 regulates mitochondrial transport and dendritic arborization in cerebellar Purkinje cells.
abstract: Mitochondria dynamically change their shape by repeated fission and fusion in response to physiological and pathological conditions. Recent studies have uncovered significant roles of mitochondrial fission and fusion in neuronal functions, such as neurotransmission and spine formation. However, the contribution of mitochondrial fission to the development of dendrites remains controversial. We analyzed the function of the mitochondrial fission GTPase Drp1 in dendritic arborization in cerebellar Purkinje cells. Overexpression of a dominant-negative mutant of Drp1 in postmitotic Purkinje cells enlarged and clustered mitochondria, which failed to exit from the soma into the dendrites. The emerging dendrites lacking mitochondrial transport remained short and unstable in culture and in vivo. The dominant-negative Drp1 affected neither the basal respiratory function of mitochondria nor the survival of Purkinje cells. Enhanced ATP supply by creatine treatment, but not reduced ROS production by antioxidant treatment, restored the hypomorphic dendrites caused by inhibition of Drp1 function. Collectively, our results suggest that Drp1 is required for dendritic distribution of mitochondria and thereby regulates energy supply in growing dendritic branches in developing Purkinje cells.
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida Honmachi, Sakyo-ku, Kyoto 606-8501, Japan; Graduate School of Biostudies, Kyoto University, Yoshida Honmachi, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kansai
authors.initials: K
authors.lastname: Fukumitsu
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida Honmachi, Sakyo-ku, Kyoto 606-8501, Japan; Graduate School of Biostudies, Kyoto University, Yoshida Honmachi, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Hatsukano
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida Honmachi, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Azumi
authors.initials: A
authors.lastname: Yoshimura
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida Honmachi, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: John
authors.initials: J
authors.lastname: Heuser
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida Honmachi, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: fujishima@icems.kyoto-u.ac.jp.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Fujishima
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida Honmachi, Sakyo-ku, Kyoto 606-8501, Japan; Graduate School of Biostudies, Kyoto University, Yoshida Honmachi, Sakyo-ku, Kyoto 606-8501, Japan. Electronic address: kengaku@icems.kyoto-u.ac.jp.
authors.forename: Mineko
authors.initials: M
authors.lastname: Kengaku
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000378:metabolism*; D055495:Neurogenesis; D011689:Purkinje Cells / Q000166:cytology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; C486391:Dnm1l protein, mouse; D034281:Dynamins
keywords: ATP; Creatine; Dendrite; Drp1; Mitochondria; Purkinje cells