Cotter Kristina, Stransky Laura, McGuire Christina, Forgac Michael
Program in Cellular and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Program in Biochemistry, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA.
Trends Biochem Sci. 2015 Oct;40(10):611-622. doi: 10.1016/j.tibs.2015.08.005.
The vacuolar (H(+))-ATPases (V-ATPases) are ATP-dependent proton pumps that acidify intracellular compartments and are also present at the plasma membrane. They function in such processes as membrane traffic, protein degradation, virus and toxin entry, bone resorption, pH homeostasis, and tumor cell invasion. V-ATPases are large multisubunit complexes, composed of an ATP-hydrolytic domain (V1) and a proton translocation domain (V0), and operate by a rotary mechanism. This review focuses on recent insights into their structure and mechanism, the mechanisms that regulate V-ATPase activity (particularly regulated assembly and trafficking), and the role of V-ATPases in processes such as cell signaling and cancer. These developments have highlighted the potential of V-ATPases as a therapeutic target in a variety of human diseases.
液泡型（H⁺）-ATP酶（V-ATP酶）是一种依赖ATP的质子泵，可使细胞内区室酸化，并且也存在于质膜上。它们在膜运输、蛋白质降解、病毒和毒素进入、骨吸收、pH稳态以及肿瘤细胞侵袭等过程中发挥作用。V-ATP酶是大型多亚基复合物，由ATP水解结构域（V1）和质子转运结构域（V0）组成，并通过旋转机制运作。本综述着重介绍了关于其结构和机制、调节V-ATP酶活性的机制（特别是调节组装和运输）以及V-ATP酶在细胞信号传导和癌症等过程中的作用的最新见解。这些进展突出了V-ATP酶作为多种人类疾病治疗靶点的潜力。
