The mitochondrial ubiquitin ligase plays an anti-apoptotic role in cardiomyocytes by regulating mitochondrial fission.
The mitochondrial ubiquitin ligase plays an anti-apoptotic role in cardiomyocytes by regulating mitochondrial fission.
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DOI：
10.1111/jcmm.12914
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发表时间：
2016-12
影响因子：
5.3
通讯作者：
Li P
中科院分区：
文献类型：
--
作者：
Wang J;Aung LH;Prabhakar BS;Li P
细胞凋亡在心肌梗死的发生发展中起着重要作用。心肌细胞富含线粒体，线粒体过度分裂可引发细胞凋亡。近年来，线粒体泛素连接酶（mitochondrial ubiquitin ligase，MITOL）被报道在线粒体动力学和细胞凋亡的调控中发挥重要作用。然而，其作用的基本机制仍不确定。本研究旨在揭示MITOL在心肌细胞凋亡调控中的作用。我们的研究结果表明，心肌细胞中MITOL表达上调，以响应凋亡刺激。线粒体泛素连接酶过表达阻断了发动蛋白相关蛋白1在线粒体中的积累，并减弱了过氧化氢诱导的线粒体分裂。相反，MITOL敲低致敏心肌细胞经历线粒体分裂，导致随后的凋亡。这些发现表明，MITOL对心肌细胞凋亡具有保护作用，并可能成为凋亡相关心脏疾病的潜在治疗靶点。
Apoptosis plays a critical role in the development of myocardial infarction. Cardiomyocytes are enriched with mitochondria and excessive mitochondrial fission can trigger cellular apoptosis. Recently, the mitochondrial ubiquitin ligase (MITOL), localized in the mitochondrial outer membrane, was reported to play an important role in the regulation of mitochondrial dynamics and apoptosis. However, the underlying mechanism of its action remains uncertain. The present study was aimed at uncovering the role of MITOL in the regulation of cardiomyocyte apoptosis. Our results showed that MITOL expression was up‐regulated in cardiomyocytes in response to apoptotic stimulation. Mitochondrial ubiquitin ligase overexpression blocked dynamin‐related protein 1 accumulation in the mitochondria, and attenuated the mitochondrial fission induced by hydrogen peroxide. Conversely, MITOL knockdown sensitized cardiomyocytes to undergo mitochondrial fission, resulting in subsequent apoptosis. These findings suggest that MITOL plays a protective role against apoptosis in cardiomyocytes, and may serve as a potential therapeutic target for apoptosis‐related cardiac diseases.
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影响因子：
4.7
作者：
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通讯作者：
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158.5
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DOI：
10.1073/pnas.95.6.2979
发表时间：
1998-03-17
影响因子：
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