Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage

Yusuke Kageyama, Zhongyan Zhang, Ricardo Roda, Masahiro Fukaya, Junko Wakabayashi, Nobunao Wakabayashi, Thomas W. Kensler, P. Hemachandra Reddy, Miho Iijima, Hiromi Sesaki

    Research output: Contribution to journalArticle

    142 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)535-551
    Number of pages17
    JournalJournal of Cell Biology
    Volume197
    Issue number4
    DOIs
    StatePublished - May 2012

    ASJC Scopus subject areas

    • Cell Biology

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  • Cite this

    Kageyama, Y., Zhang, Z., Roda, R., Fukaya, M., Wakabayashi, J., Wakabayashi, N., Kensler, T. W., Hemachandra Reddy, P., Iijima, M., & Sesaki, H. (2012). Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. Journal of Cell Biology, 197(4), 535-551. https://doi.org/10.1083/jcb.201110034