摘要
背景:电压依赖性阴离子通道1(VDAC1)是线粒体外膜蛋白,作为线粒体调控者,控制代谢物进出线粒体和能量生成,同时协调糖酵解和氧化磷酸化。 VDAC1在线粒体介导的细胞凋亡中起关键作用,其通过在位于膜间隙中的凋亡蛋白的释放以及由于其与促凋亡蛋白和抗凋亡蛋白的结合而起作用。因此,VDAC1被认为是控制凋亡的有希望的靶标。 方法:我们回顾了已发表的数据,提供了累积的证据,表明VDAC1寡聚化代表了线粒体内在介导的凋亡途径中的重要步骤。 结果:公布的数据支持VDAC1寡聚化导致形成允许促细胞凋亡蛋白释放到胞质溶胶中从而激活细胞凋亡的大孔的提议。提出了VDAC1表达水平与细胞凋亡诱导之间关系的证据。这包括几乎所有细胞凋亡刺激都诱导VDAC1过表达将VDAC1从单体转变为寡聚体组装,对应于Cyto c释放通道。提出了诱导VDAC1过表达,VDAC1寡聚化和细胞凋亡的复合物或条件。同样,VDAC1相互作用分子,既抑制VDAC1寡聚化和细胞凋亡也提出。 结论:本综述重点介绍了VDAC1寡聚化作为控制细胞凋亡的潜在靶点,特别是使用药物诱导癌细胞凋亡性细胞死亡,抑制神经退行性疾病的凋亡以及VDAC1治疗应用的可能性。
关键词: 细胞凋亡,线粒体,寡聚化,VDAC1,糖基化,氧化磷酸化。
Current Medicinal Chemistry
Title:VDAC1 as a Player in Mitochondria-Mediated Apoptosis and Target for Modulating Apoptosis
Volume: 24 Issue: 40
关键词: 细胞凋亡,线粒体,寡聚化,VDAC1,糖基化,氧化磷酸化。
摘要: Background: The voltage-dependent anion channel 1 (VDAC1), an outer mitochondria membrane protein, functions as a mitochondrial governor, controlling transport of metabolites in and out of the mitochondria and energy production, while also coordinating glycolysis and oxidative phosphorylation. VDAC1 plays a key role in mitochondria-mediated apoptosis by functioning in the release of apoptotic proteins located in the inter-membranal space and due to its association with pro- and anti-apoptotic proteins. Thus, VDAC1 is considered as a promising target for controlling apoptosis.
Methods: We reviewed published data presenting accumulated evidence suggesting that VDAC1 oligomerization represents an important step in the intrinsic mitochondria-mediated apoptosis pathway.
Results: The published data support the proposal that VDAC1 oligomerization leads to the formation of a large pore that allows the release of pro-apoptotic proteins to the cytosol, thereby, activation of apoptosis. Evidence for the relationship between VDAC1 expression levels and induction of apoptosis are presented. This includes the finding that almost all apoptosis stimuli induce VDAC1 over-expression shifting VDAC1 from a monomeric to an oligomeric assembly, corresponding to the Cyto c release channel. Copounds or conditions inducing VDAC1 over-expression, VDAC1 oligomerization and apoptosis are presented. Likewise, VDAC1-interacting molecules, that inhibit both VDAC1 oligomerization and apoptosis are also presented.
Conclusion: This review highlights the findings about VDAC1 oligomerization as a potential target for controlling apoptosis, specifically using drugs to induce apoptotic cell death in cancer and inhibit apoptosis in neurodegenerative diseases, as well as possible VDAC1-based therapeutic applications.
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Cite this article as:
VDAC1 as a Player in Mitochondria-Mediated Apoptosis and Target for Modulating Apoptosis, Current Medicinal Chemistry 2017; 24 (40) . https://dx.doi.org/10.2174/0929867324666170616105200
DOI https://dx.doi.org/10.2174/0929867324666170616105200 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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