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

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

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Purkinje Cells
Neurons
Mitochondria
Mitochondrial Degradation
Mitochondrial Dynamics
Mitochondrial Swelling
Gene Knockout Techniques
Ubiquitin-Protein Ligases
Ubiquitination
Mitochondrial Proteins
Ubiquitin
Neurodegenerative Diseases
Quality Control
Cerebellum
Hydrogen Peroxide
Cell Death
Fibroblasts
Antioxidants

ASJC Scopus subject areas

  • Cell Biology

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Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. / Kageyama, Yusuke; Zhang, Zhongyan; Roda, Ricardo; Fukaya, Masahiro; Wakabayashi, Junko; Wakabayashi, Nobunao; Kensler, Thomas W; Hemachandra Reddy, P.; Iijima, Miho; Sesaki, Hiromi.

In: Journal of Cell Biology, Vol. 197, No. 4, 05.2012, p. 535-551.

Research output: Contribution to journalArticle

Kageyama, Yusuke ; Zhang, Zhongyan ; Roda, Ricardo ; Fukaya, Masahiro ; Wakabayashi, Junko ; Wakabayashi, Nobunao ; Kensler, Thomas W ; Hemachandra Reddy, P. ; Iijima, Miho ; Sesaki, Hiromi. / Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage. In: Journal of Cell Biology. 2012 ; Vol. 197, No. 4. pp. 535-551.
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