Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage.
Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage.
复制标题
DOI：
10.1083/jcb.201110034
复制
发表时间：
2012-05-14
期刊：
影响因子：
--
通讯作者：
Sesaki H
中科院分区：
文献类型：
--
作者：
Kageyama Y;Zhang Z;Roda R;Fukaya M;Wakabayashi J;Wakabayashi N;Kensler TW;Reddy PH;Iijima M;Sesaki H
线粒体分裂作为一种质量控制机制来抑制氧化损伤，从而促进神经元存活。线粒体不断分裂和融合，这两个过程之间的平衡调节线粒体的形状。线粒体动力学的改变与神经退行性疾病有关。在这里，我们调查的生理和细胞功能的线粒体分裂在有丝分裂后的神经元使用在体内和体外基因敲除的线粒体分裂蛋白Drp1。当小鼠Drp1在小脑的有丝分裂后浦肯野细胞中被删除时，线粒体小管由于过度融合而伸长，由于氧化损伤而变成大球体，积累了泛素和线粒体自噬标记物，并失去了呼吸功能，导致神经退行性变。线粒体的泛素化是独立的E3泛素连接酶parkin在浦肯野细胞缺乏Drp1。抗氧化剂治疗挽救了Drp1KO Purkinje细胞的线粒体肿胀和细胞死亡。此外，过氧化氢将Drp1KO成纤维细胞中的细长小管转化为大球体。我们的研究结果表明，线粒体分裂作为一种质量控制机制，以抑制氧化损伤，从而促进神经元的生存。
Mitochondrial division serves as a quality control mechanism to suppress oxidative damage and thus promote neuronal survival. 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.
登录
查看更多内容
影响因子：
64.5
作者：
Chen H;Vermulst M;Wang YE;Chomyn A;Prolla TA;McCaffery JM;Chan DC
通讯作者：
Chan DC
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC
影响因子：
5.2
作者：
Chang CR;Blackstone C
通讯作者：
Blackstone C
影响因子：
4.8
作者：
James, DI;Parone, PA;Martinou, JC
通讯作者：
Martinou, JC
影响因子：
64.5
作者：
Li, Z;Okamoto, K;Sheng, M
通讯作者：
Sheng, M