title: Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage.
abstract: Mitochondria divide and fuse continuously, and the balance between these two processes regulates mitochondrial shape. Alterations in mitochondrial dynamics are associated with neurodegenerative diseases. Here we investigate the physiological and cellular functions of mitochondrial division in postmitotic neurons using in vivo and in vitro gene knockout for the mitochondrial division protein Drp1. When mouse Drp1 was deleted in postmitotic Purkinje cells in the cerebellum, mitochondrial tubules elongated due to excess fusion, became large spheres due to oxidative damage, accumulated ubiquitin and mitophagy markers, and lost respiratory function, leading to neurodegeneration. Ubiquitination of mitochondria was independent of the E3 ubiquitin ligase parkin in Purkinje cells lacking Drp1. Treatment with antioxidants rescued mitochondrial swelling and cell death in Drp1KO Purkinje cells. Moreover, hydrogen peroxide converted elongated tubules into large spheres in Drp1KO fibroblasts. Our findings suggest that mitochondrial division serves as a quality control mechanism to suppress oxidative damage and thus promote neuronal survival.
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kageyama
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ricardo
authors.initials: R
authors.lastname: Roda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukaya
authors.forename: Junko
authors.initials: J
authors.lastname: Wakabayashi
authors.forename: Nobunao
authors.initials: N
authors.lastname: Wakabayashi
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Kensler
authors.forename: P Hemachandra
authors.initials: PH
authors.lastname: Reddy
authors.forename: Miho
authors.initials: M
authors.lastname: Iijima
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sesaki
mesh_terms: D000818:Animals; D002470:Cell Survival; D034281:Dynamins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008938:Mitosis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010084:Oxidation-Reduction; D011689:Purkinje Cells / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; C486391:Dnm1l protein, mouse; D034281:Dynamins