Mitochondrial binding of α-enolase stabilizes mitochondrial membrane: Its role in doxorubicin-induced cardiomyocyte apoptosis
Mitochondrial binding of α-enolase stabilizes mitochondrial membrane: Its role in doxorubicin-induced cardiomyocyte apoptosis
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DOI：
10.1016/j.abb.2013.12.008
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发表时间：
2014-01-15
影响因子：
3.9
通讯作者：
Liu, Pei-qing
中科院分区：
文献类型：
--
作者：
Gao, Si;Li, Hong;Liu, Pei-qing
α-烯醇化酶是分解代谢糖酵解途径中的代谢酶。在真核细胞中，α-烯醇化酶的亚细胞区室化以及其多方面的功能已被确定。在这里，我们报告说，α-烯醇化酶是一个调节器的心脏线粒体，它部分位于大鼠心肌细胞的线粒体。多柔比星处理从线粒体置换α-烯醇化酶，伴随着线粒体的活化（细胞死亡途径。此外，在分离的线粒体，重组cccenolase显着减轻Ca 2+诱导的膜电位的损失，基质肿胀和膜透性。相反，α-烯醇化酶敲低H9 c2成肌细胞的线粒体在Ca 2+刺激后经历了更严重的膜去极化和肿胀。此外，α-烯醇化酶被进一步鉴定为与线粒体外膜中的电压依赖性阴离子通道1相互作用，该通道被多柔比星削弱。总的来说，本研究表明，α-烯醇化酶在稳定线粒体膜中具有有益的作用。在心肌细胞中，阿霉素从线粒体中置换α-烯醇化酶可能涉及内在细胞死亡途径的激活。(C)2013 Elsevier Inc. All rights reserved.
alpha-Enolase is a metabolic enzyme in the catabolic glycolytic pathway. In eukaryotic cells, the subcellular compartmentalization of alpha-enolase as well as its multifaceted functions has been identified. Here, we report that alpha-enolase is a regulator of cardiac mitochondria; it partially located in the mitochondria of rat cardiomyocytes. Doxorubicin treatment displaced alpha-enolase from mitochondria, accompanied by activation of mitochondria( cell death pathway. Furthermore, in isolated mitochondria, recombinant ccenolase significantly alleviated Ca2+-induced loss of membrane potential, swelling of matrix and permeabilization of membrane. In contrast, mitochondria from alpha-enolase knockdown H9c2 myoblasts underwent more severe membrane depolarization and swelling after Ca2+ stimulation. In addition, alpha-enolase was further identified to interact with voltage dependent anion channel 1 in the outer membrane of mitochondria, which was weakened by doxorubicin. Collectively, the present study indicates that mitochondria-located alpha-enolase has a beneficial role in stabilizing mitochondrial membrane. In cardiomyocytes, the displacement of alpha-enolase from mitochondria by doxorubicin may involve in activation of the intrinsic cell death pathway. (C) 2013 Elsevier Inc. All rights reserved.