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线粒体细胞器作为潜在治疗靶点的动力学。

The dynamics of the mitochondrial organelle as a potential therapeutic target.

机构信息

State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University Shanghai Medical College, Shanghai, China.

出版信息

J Cereb Blood Flow Metab. 2013 Jan;33(1):22-32. doi: 10.1038/jcbfm.2012.158. Epub 2012 Oct 24.

Abstract

Mitochondria play a central role in cell fate after stressors such as ischemic brain injury. The convergence of intracellular signaling pathways on mitochondria and their release of critical factors are now recognized as a default conduit to cell death or survival. Besides the individual processes that converge on or emanate from mitochondria, a mitochondrial organellar response to changes in the cellular environment has recently been described. Whereas mitochondria have previously been perceived as a major center for cellular signaling, one can postulate that the organelle's dynamics themselves affect cell survival. This brief perspective review puts forward the concept that disruptions in mitochondrial dynamics--biogenesis, clearance, and fission/fusion events--may underlie neural diseases and thus could be targeted as neuroprotective strategies in the context of ischemic injury. To do so, we present a general overview of the current understanding of mitochondrial dynamics and regulation. We then review emerging studies that correlate mitochondrial biogenesis, mitophagy, and fission/fusion events with neurologic disease and recovery. An overview of the system as it is currently understood is presented, and current assessment strategies and their limitations are discussed.

摘要

线粒体在应激后(如脑缺血损伤)的细胞命运中起着核心作用。现在人们认识到,细胞内信号通路在细胞内的汇聚以及线粒体释放关键因子是细胞死亡或存活的默认途径。除了汇聚于线粒体或从线粒体发散的单个过程外,最近还描述了线粒体对细胞环境变化的细胞器反应。虽然线粒体以前被认为是细胞信号的主要中心,但人们可以假设细胞器的动力学本身会影响细胞的存活。这篇简短的观点综述提出了这样一种概念,即线粒体动力学(生物发生、清除和分裂/融合事件)的中断可能是神经疾病的基础,因此在缺血损伤的情况下,线粒体动力学的中断可能成为神经保护策略的靶点。为此,我们对线粒体动力学和调节的现有理解进行了概述。然后,我们回顾了与神经疾病和恢复相关的线粒体生物发生、线粒体自噬和分裂/融合事件的新兴研究。本文介绍了目前对该系统的理解,并讨论了当前的评估策略及其局限性。

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