Mitochondria and mitophagy: the yin and yang of cell death control.
Mitochondria and mitophagy: the yin and yang of cell death control.
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DOI：
10.1161/circresaha.112.265819
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发表时间：
2012-10-12
影响因子：
20.1
通讯作者：
Gustafsson ÅB
中科院分区：
文献类型：
--
作者：
Kubli DA;Gustafsson ÅB
线粒体主要负责为收缩的心肌细胞提供连续的ATP供应。然而，线粒体可以迅速变成促进死亡的细胞器。响应于细胞内环境的变化，线粒体成为过量活性氧物质的生产者并释放促死亡蛋白，导致ATP合成中断和细胞死亡途径的激活。有趣的是，细胞已经发展出一种防御机制，以对抗可能对细胞造成伤害的异常线粒体。这种机制涉及选择性隔离和随后的降解功能障碍的细胞因子之前，它导致细胞死亡的激活。诱导线粒体自噬或线粒体自噬，导致细胞中受损线粒体的选择性清除。响应于应激，例如缺血/再灌注，促存活和促死亡途径在心肌细胞中伴随激活。因此，在应激过程中，心肌细胞的生与死之间存在着微妙的平衡，最终的结果取决于这些通路之间复杂的串扰。线粒体自噬作为一种早期的心脏保护反应发挥作用，通过清除受损的线粒体有利于适应压力。相反，增加的氧化应激和凋亡蛋白酶可使有丝分裂吞噬失活，从而导致细胞死亡。在此，我们讨论了线粒体和线粒体自噬在心血管健康和疾病中的重要性，并对我们目前对这些过程如何在心肌中调节的理解进行了综述。
Mitochondria are primarily responsible for providing the contracting cardiac myocyte with a continuous supply of ATP. However, mitochondria can rapidly change into death-promoting organelles. In response to changes in the intracellular environment, mitochondria become producers of excessive reactive oxygen species and release pro-death proteins, resulting in disrupted ATP synthesis and activation of cell death pathways. Interestingly, cells have developed a defense mechanism against aberrant mitochondria that can cause harm to the cell. This mechanism involves selective sequestration and subsequent degradation of the dysfunctional mitochondrion before it causes activation of cell death. Induction of mitochondrial autophagy, or mitophagy, results in selective clearance of damaged mitochondria in cells. In response to stress such as ischemia/reperfusion, pro-survival and pro-death pathways are concomitantly activated in cardiac myocytes. Thus, there is a delicate balance between life and death in the myocytes during stress, and the final outcome depends on the complex crosstalk between these pathways. Mitophagy functions as an early cardioprotective response, favoring adaptation to stress by removing damaged mitochondria. In contrast, increased oxidative stress and apoptotic proteases can inactivate mitophagy, allowing for the execution of cell death. Herein, we discuss the importance of mitochondria and mitophagy in cardiovascular health and disease, and provide a review of our current understanding of how these processes are regulated in the myocardium.