Transgenic control of mitochondrial fission induces mitochondrial uncoupling and relieves diabetic oxidative stress.
Transgenic control of mitochondrial fission induces mitochondrial uncoupling and relieves diabetic oxidative stress.
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作者：
Galloway CA;Lee H;Nejjar S;Jhun BS;Yu T;Hsu W;Yoon Y
线粒体是产生大多数细胞能量的重要真核细胞器。线粒体的能量产生和供应似乎与由分裂和融合介导的线粒体的持续形态变化密切相关，这不仅由分裂/融合基因的突变所导致的遗传性疾病所证明，也由与众多病理损伤相关的异常线粒体形态所证明。然而，线粒体的形态变化如何与其产能量活动相关联却知之甚少。在这项研究中，我们发现线粒体分裂的扰动通过线粒体内膜电位的大规模波动诱导一种独特的线粒体解偶联现象。此外，通过基因控制线粒体分裂从而在小鼠中诱导轻微的质子泄漏，我们能够使这些小鼠在高血糖模型中免受氧化应激。这些发现为线粒体分裂如何参与调节线粒体活动提供了机制上的见解。此外，这些结果表明线粒体分裂在许多人类疾病中控制线粒体活性氧产生和氧化应激方面具有潜在应用。
Mitochondria are the essential eukaryotic organelles that produce most cellular energy. The energy production and supply by mitochondria appear closely associated with the continuous shape change of mitochondria mediated by fission and fusion, as evidenced not only by the hereditary diseases caused by mutations in fission/fusion genes but also by aberrant mitochondrial morphologies associated with numerous pathologic insults. However, how morphological change of mitochondria is linked to their energy-producing activity is poorly understood. In this study, we found that perturbation of mitochondrial fission induces a unique mitochondrial uncoupling phenomenon through a large-scale fluctuation of a mitochondrial inner membrane potential. Furthermore, by genetically controlling mitochondrial fission and thereby inducing mild proton leak in mice, we were able to relieve these mice from oxidative stress in a hyperglycemic model. These findings provide mechanistic insight into how mitochondrial fission participates in regulating mitochondrial activity. In addition, these results suggest a potential application of mitochondrial fission to control mitochondrial reactive oxygen species production and oxidative stress in many human diseases.
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影响因子：
64.5
作者：
Ichas, F;Jouaville, LS;Mazat, JP
通讯作者：
Mazat, JP
影响因子：
4
作者：
De Giorgi, F;Lartigue, L;Ichas, F
通讯作者：
Ichas, F
影响因子：
7.7
作者：
Deng, SP;Vatamaniuk, M;Markmann, JF
通讯作者：
Markmann, JF
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：
7.7
作者：
Baynes, JW;Thorpe, SR
通讯作者：
Thorpe, SR