TY - JOUR
T1 - Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage
AU - Kageyama, Yusuke
AU - Zhang, Zhongyan
AU - Roda, Ricardo
AU - Fukaya, Masahiro
AU - Wakabayashi, Junko
AU - Wakabayashi, Nobunao
AU - Kensler, Thomas W.
AU - Hemachandra Reddy, P.
AU - Iijima, Miho
AU - Sesaki, Hiromi
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.201110034
DO - 10.1083/jcb.201110034
M3 - Article
C2 - 22564413
AN - SCOPUS:84862605918
SN - 0021-9525
VL - 197
SP - 535
EP - 551
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -