Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Biomolecules. 2020 Oct 26;10(11):1485. doi: 10.3390/biom10111485.
The voltage-dependent anion channel 1 (VDAC1) protein, is an important regulator of mitochondrial function, and serves as a mitochondrial gatekeeper, with responsibility for cellular fate. In addition to control over energy sources and metabolism, the protein also regulates epigenomic elements and apoptosis via mediating the release of apoptotic proteins from the mitochondria. Apoptotic and pathological conditions, as well as certain viruses, induce cell death by inducing VDAC1 overexpression leading to oligomerization, and the formation of a large channel within the VDAC1 homo-oligomer. This then permits the release of pro-apoptotic proteins from the mitochondria and subsequent apoptosis. Mitochondrial DNA can also be released through this channel, which triggers type-Ι interferon responses. VDAC1 also participates in endoplasmic reticulum (ER)-mitochondria cross-talk, and in the regulation of autophagy, and inflammation. Its location in the outer mitochondrial membrane, makes VDAC1 ideally placed to interact with over 100 proteins, and to orchestrate the interaction of mitochondrial and cellular activities through a number of signaling pathways. Here, we provide insights into the multiple functions of VDAC1 and describe its involvement in several diseases, which demonstrate the potential of this protein as a druggable target in a wide variety of pathologies, including cancer.
电压依赖性阴离子通道 1（VDAC1）蛋白是一种重要的线粒体功能调节剂，作为线粒体的守门员，负责细胞命运。除了控制能量来源和代谢外，该蛋白还通过介导凋亡蛋白从线粒体释放来调节表观遗传元件和细胞凋亡。凋亡和病理条件以及某些病毒通过诱导 VDAC1 过表达导致寡聚化和 VDAC1 同源寡聚体中形成大通道来诱导细胞死亡。这允许促凋亡蛋白从线粒体中释放并随后发生细胞凋亡。线粒体 DNA 也可以通过该通道释放，从而引发 I 型干扰素反应。VDAC1 还参与内质网（ER）-线粒体相互作用以及自噬和炎症的调节。其位于线粒体外膜上，使 VDAC1 能够与超过 100 种蛋白质相互作用，并通过多种信号通路协调线粒体和细胞活动的相互作用。在这里，我们深入探讨了 VDAC1 的多种功能，并描述了它在几种疾病中的参与，这表明该蛋白作为多种病理情况下（包括癌症）的药物靶点具有潜力。
