Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
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DOI：
10.1042/bj20111451
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发表时间：
2012-01-15
期刊：
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Lee J;Giordano S;Zhang J
活性氧和氮通过不同的机制改变细胞反应，现在正在定义。在低水平时，它们是信号分子，在高水平时，它们会破坏细胞器，特别是线粒体。氧化损伤和相关的线粒体功能障碍可导致能量消耗、细胞毒性介质的积累和细胞死亡。了解应激适应和细胞死亡之间的界面对于理解氧化还原生物学和疾病发病机制非常重要。最近的研究发现，在细胞反应中，氧化还原信号的一个主要传感器是自噬。自噬活性由复杂的分子机制介导，包括超过30种Atg（AutophaGy相关）蛋白和50种溶酶体水解酶。自噬体形成膜结构，隔离受损、氧化或功能失调的细胞内组分和细胞器，并将它们引导至溶酶体进行降解。这种自噬过程是线粒体更新的唯一已知机制。据推测，自噬功能障碍可能导致线粒体功能异常和氧化或硝化应激。新兴的研究提供了线粒体自噬（也称为线粒体自噬）是如何控制的新的理解，以及自噬功能障碍对细胞氧化应激的影响。本综述强调了最近的研究氧化还原信号在自噬的调节，在线粒体自噬的基本机制的背景下。此外，我们还讨论了自噬对线粒体功能和活性物质积累的影响。这与退行性疾病特别相关，其中氧化应激随时间发生，线粒体和自噬途径中的功能障碍起作用。
Reactive oxygen and nitrogen species change cellular responses through diverse mechanisms that are now being defined. At low levels, they are signalling molecules, and at high levels, they damage organelles, particularly the mitochondria. Oxidative damage and the associated mitochondrial dysfunction may result in energy depletion, accumulation of cytotoxic mediators and cell death. Understanding the interface between stress adaptation and cell death then is important for understanding redox biology and disease pathogenesis. Recent studies have found that one major sensor of redox signalling at this switch in cellular responses is autophagy. Autophagic activities are mediated by a complex molecular machinery including more than 30 Atg (AuTophaGy-related) proteins and 50 lysosomal hydrolases. Autophagosomes form membrane structures, sequester damaged, oxidized or dysfunctional intracellular components and organelles, and direct them to the lysosomes for degradation. This autophagic process is the sole known mechanism for mitochondrial turnover. It has been speculated that dysfunction of autophagy may result in abnormal mitochondrial function and oxidative or nitrative stress. Emerging investigations have provided new understanding of how autophagy of mitochondria (also known as mitophagy) is controlled, and the impact of autophagic dysfunction on cellular oxidative stress. The present review highlights recent studies on redox signalling in the regulation of autophagy, in the context of the basic mechanisms of mitophagy. Furthermore, we discuss the impact of autophagy on mitochondrial function and accumulation of reactive species. This is particularly relevant to degenerative diseases in which oxidative stress occurs over time, and dysfunction in both the mitochondrial and autophagic pathways play a role.