Mitochondrial VDAC1: A Key Gatekeeper as Potential Therapeutic Target.
Mitochondrial VDAC1: A Key Gatekeeper as Potential Therapeutic Target.
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DOI：
10.3389/fphys.2017.00460
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发表时间：
2017
影响因子：
4
通讯作者：
Kwok WM
中科院分区：
文献类型：
--
作者：
Camara AKS;Zhou Y;Wen PC;Tajkhorshid E;Kwok WM
线粒体是ATP的关键来源，其为细胞功能提供燃料，并且它们在细胞信号传导、细胞分裂和凋亡中也是中心的。线粒体的功能障碍与广泛的疾病有关，包括神经退行性疾病和心脏疾病以及各种类型的癌症。调节线粒体功能的关键蛋白质之一是电压依赖性阴离子通道1（VDAC 1），它是线粒体外膜上最丰富的蛋白质。VDAC 1是代谢物、核苷酸和离子通道的守门人;由于其与凋亡和抗凋亡蛋白（即Bcl-2蛋白家族和己糖激酶的成员）相互作用，其在调节细胞凋亡中起着至关重要的作用。因此，VDAC 1的调节不仅对线粒体的代谢功能至关重要，而且对细胞存活也至关重要。事实上，多种证据证实VDAC 1参与了多种疾病。因此，VDAC 1功能的调节或失调可能会减弱或加重病理生理学状况。了解VDAC 1在健康和疾病中的作用可能会导致选择性保护不同组织和不同疾病中的细胞。本综述的目的是讨论VDAC 1在疾病发病机制中的作用，以及作为各种病理学治疗管理的潜在有效靶点。
Mitochondria are the key source of ATP that fuels cellular functions, and they are also central in cellular signaling, cell division and apoptosis. Dysfunction of mitochondria has been implicated in a wide range of diseases, including neurodegenerative and cardiac diseases, and various types of cancer. One of the key proteins that regulate mitochondrial function is the voltage-dependent anion channel 1 (VDAC1), the most abundant protein on the outer membrane of mitochondria. VDAC1 is the gatekeeper for the passages of metabolites, nucleotides, and ions; it plays a crucial role in regulating apoptosis due to its interaction with apoptotic and anti-apoptotic proteins, namely members of the Bcl-2 family of proteins and hexokinase. Therefore, regulation of VDAC1 is crucial not only for metabolic functions of mitochondria, but also for cell survival. In fact, multiple lines of evidence have confirmed the involvement of VDAC1 in several diseases. Consequently, modulation or dysregulation of VDAC1 function can potentially attenuate or exacerbate pathophysiological conditions. Understanding the role of VDAC1 in health and disease could lead to selective protection of cells in different tissues and diverse diseases. The purpose of this review is to discuss the role of VDAC1 in the pathogenesis of diseases and as a potentially effective target for therapeutic management of various pathologies.