Mitochondria and ischemia/reperfusion injury
Mitochondria and ischemia/reperfusion injury
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DOI：
10.1196/annals.1341.022
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Weiss, JN
中科院分区：
文献类型：
--
作者：
Honda, HM;Korge, P;Weiss, JN
心脏缺血/再灌注损伤导致细胞凋亡、坏死和正常组织的可变混合，这取决于缺血的持续时间和严重程度。损伤可以通过缺血预处理和药物预处理激活保护途径来消除。线粒体作为细胞生死的最终仲裁者，因为这些细胞器不仅需要产生ATP，而且还可以触发细胞凋亡或坏死。线粒体损伤的一个关键机制是线粒体通透性转换（MPT），已被证明发生在再灌注。文章假设缺血/再灌注促进MPT分两个阶段：（1）缺血期间MPT启动发生，因为在脂肪酸积累和细胞色素c和抗氧化剂损失的情况下，进行性线粒体内膜泄漏伴随着电子传递抑制;（2）再灌注时MPT的触发由线粒体膜电位（Delta Psi（m））的相互作用决定。已经发现，促进线粒体恢复的策略，如二氮嗪的药理学预处理，是由基质体积和Δ Psi（m）的K+依赖性调节介导的，导致ATP合成效率的提高以及细胞色素c损失的预防。如果线粒体不能恢复，则MPT和过度挛缩可导致Δ Psi（m）。去极化波再生地穿过细胞（0.1至0.2 μ m/s）。
Cardiac ischemia/reperfusion injury results in a variable mixture of apoptotic, necrotic, and normal tissue that depends on both the duration and severity of ischemia. Injury can be abrogated by activation of protective pathways via ischemic and pharmacologic preconditioning. Mitochondria serve as final arbiters of life and death of the cell as these organelles not only are required to generate ATP but also can trigger apoptosis or necrosis. A key mechanism of mitochondrial injury is by the mitochondrial permeability transition (MPT) that has been shown to occur at reperfusion. The article hypothesizes that ischemia/reperfusion promotes MPT in two phases: (1) MPT priming during ischemia occurs as progressive inner mitochondrial membrane leak is accompanied by depressed electron transport in the setting of fatty acid accumulation and loss of cytochrome c and antioxidants; and (2) Triggering of MPT at reperfusion is determined by the interplay of mitochondrial membrane potential (Delta Psi(m).) with mitochondrial matrix Ca, reactive oxygen species, and pH. It has been found that strategies that promote mitochondrial recovery such as pharmacologic preconditioning by diazoxide are mediated by K+-dependent regulation of matrix volume and Delta Psi(m), resulting in improved efficiency of ATP synthesis as well as prevention of cytochrome c loss. If mitochondria fail to recover, then MPT and hypercontracture can result as Delta Psi(m). depolarization waves regeneratively cross the cell (0.1 to 0.2 mu m/s).