Mitochondrial pruning by Nix and BNip3: an essential function for cardiac-expressed death factors.
Mitochondrial pruning by Nix and BNip3: an essential function for cardiac-expressed death factors.
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DOI：
10.1007/s12265-010-9174-x
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发表时间：
2010-08
影响因子：
3.4
通讯作者：
Dorn GW 2nd
中科院分区：
文献类型：
--
作者：
Dorn GW 2nd
通过内在途径或线粒体途径的程序性心肌细胞死亡是心肌梗死后和慢性压力超负荷肥大期间病理性心室重构的机制。在缺血心肌和肥厚心肌中，密切相关的促凋亡Bcl 2家族成员BNip 3和Nix的转录上调表明，心脏应激可以启动程序性细胞死亡并导致扩张型心肌病的分子机制。随后使用转基因和基因敲除小鼠的研究表明，BNip3和Nix的表达对于心肌病的发展是足够的，并且对于可逆性冠状动脉闭塞和横向主动脉结扎后的心脏重塑是必要的。在这里，这些数据进行审查的背景下，最近的研究结果表明，尼克斯不仅刺激心肌细胞凋亡，但也诱导线粒体自噬（mitophagy），间接激活线粒体通透性转换孔，导致细胞坏死。新的研究结果表明，Nix和BNip3具有重要的功能，“线粒体修剪”，抑制心肌细胞中的线粒体增殖，没有它，年龄依赖性线粒体心肌病的发展。
Programmed cardiac myocyte death via the intrinsic, or mitochondrial, pathway is a mechanism of pathological ventricular remodeling after myocardial infarction and during chronic pressure overload hypertrophy. Transcriptional upregulation of the closely related proapoptotic Bcl2 family members BNip3 in ischemic myocardium and Nix in hypertrophied myocardium suggested a molecular mechanism by which programmed cell death can be initiated by cardiac stress and lead to dilated cardiomyopathy. Studies using transgenic and gene knockout mice subsequently demonstrated that expression of BNip3 and Nix is both sufficient for cardiomyopathy development and necessary for cardiac remodeling after reversible coronary occlusion and transverse aortic banding, respectively. Here, these data are reviewed in the context of recent findings showing that Nix not only stimulates cardiomyocyte apoptosis but also induces mitochondrial autophagy (mitophagy) and indirectly activates the mitochondrial permeability transition pore, causing cell necrosis. New findings are presented suggesting that Nix and BNip3 have an essential function, “mitochondrial pruning,” that restrains mitochondrial proliferation in cardiomyocytes and without which an age-dependent mitochondrial cardiomyopathy develops.
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影响因子：
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作者：
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