Mitochondrial function in hypoxic ischemic injury and influence of aging.
Mitochondrial function in hypoxic ischemic injury and influence of aging.
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DOI：
10.1016/j.pneurobio.2016.06.006
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发表时间：
2017-10
影响因子：
6.7
通讯作者：
Raju, Raghavan
中科院分区：
文献类型：
--
作者：
Ham, P. Benson, III;Raju, Raghavan
关键词：
Ischemia/reperfusionHypoxiaMitokineOxidative phosphorylationResveratrol, SIRT1, sirtuinsMitoquinoneTempolBlood brain barrierTunneling nanotubeNuclear-mitochondria cross-talkIntermitochondrial signal propagationPseudohypoxiaStroke, myocardial infarctionAlzheimer's diseaseParkinson's diseaseAutophagyApoptosis
线粒体是缺氧/缺血损伤的主要靶点。线粒体损伤随着年龄的增长而增加，导致与线粒体相关的分子途径失调。老年人缺氧缺血性损伤后线粒体稳态和细胞能量学的紊乱影响预后。在急性损伤条件下，细胞机制依赖于通过调节翻译后修饰的快速适应。因此，低氧诱导因子1α（HIF-1α）、过氧化物酶体增殖物激活受体γ共激活因子α（PGC-1α）、c-MYC、SIRT 1和AMPK等分子介导物的翻译后调节在缺氧缺血条件下糖酵解-线粒体能量轴的调控中发挥关键作用。氧气和营养物质的缺乏导致对线粒体的能量依赖降低，促进糖酵解。假性缺氧、自噬下降和应激反应失调与衰老的结合增加了宿主对缺氧缺血性损伤的反应。此外，线粒体信号传播和线粒体代谢中响应于氧化应激的组织范围振荡正在成为细胞能量学的重要组成部分。最近报道的线粒体通过隧道纳米管的细胞间运输也在缺血性损伤的反应和治疗中发挥作用。在这篇综述中，我们试图提供一个概述的分子机制和潜在的治疗方法与衰老和损伤的细胞能量学的改变与神经生物学的角度。
Mitochondria are a major target in hypoxic/ischemic injury. Mitochondrial impairment increases with age leading to dysregulation of molecular pathways linked to mitochondria. The perturbation of mitochondrial homeostasis and cellular energetics worsens outcome following hypoxic-ischemic insults in elderly individuals. In response to acute injury conditions, cellular machinery relies on rapid adaptations by modulating posttranslational modifications. Therefore, post-translational regulation of molecular mediators such as hypoxia-inducible factor 1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator α (PGC-1α), c-MYC, SIRT1 and AMPK play a critical role in the control of the glycolytic-mitochondrial energy axis in response to hypoxic-ischemic conditions. The deficiency of oxygen and nutrients leads to decreased energetic reliance on mitochondria, promoting glycolysis. The combination of pseudohypoxia, declining autophagy, and dysregulation of stress responses with aging adds to impaired host response to hypoxic-ischemic injury. Furthermore, intermitochondrial signal propagation and tissue wide oscillations in mitochondrial metabolism in response to oxidative stress are emerging as vital to cellular energetics. Recently reported intercellular transport of mitochondria through tunneling nanotubes also play a role in the response to and treatments for ischemic injury. In this review we attempt to provide an overview of some of the molecular mechanisms and potential therapies involved in the alteration of cellular energetics with aging and injury with a neurobiological perspective.
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DOI：
10.1073/pnas.0307156101
发表时间：
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影响因子：
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发表时间：
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影响因子：
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