文章：

V-ATP酶在癌症和细胞死亡中的作用

The V-ATPases in cancer and cell death 

原文发布日期：2022-05-03 

英文摘要：

Transmembrane ATPases are membrane-bound enzyme complexes and ion transporters that can be divided into F-, V-, and A-ATPases according to their structure. The V-ATPases, also known as H+-ATPases, are large multi-subunit protein complexes composed of a peripheral domain (V1) responsible for the hydrolysis of ATP and a membrane-integrated domain (V0) that transports protons across plasma membrane or organelle membrane. V-ATPases play a fundamental role in maintaining pH homeostasis through lysosomal acidification and are involved in modulating various physiological and pathological processes, such as macropinocytosis, autophagy, cell invasion, and cell death (e.g., apoptosis, anoikis, alkaliptosis, ferroptosis, and lysosome-dependent cell death). In addition to participating in embryonic development, V-ATPase pathways, when dysfunctional, are implicated in human diseases, such as neurodegenerative diseases, osteopetrosis, distal renal tubular acidosis, and cancer. In this review, we summarize the structure and regulation of isoforms of V-ATPase subunits and discuss their context-dependent roles in cancer biology and cell death. Updated knowledge about V-ATPases may enable us to design new anticancer drugs or strategies. 

摘要翻译： 

跨膜ATP酶是一类膜结合酶复合物和离子转运体，根据结构可分为F型、V型和A型ATP酶。V型ATP酶（又称H+-ATP酶）是由负责ATP水解的外周结构域（V1）与参与质膜或细胞器膜质子转运的膜整合结构域（V0）组成的大型多亚基蛋白复合物。V型ATP酶通过溶酶体酸化在维持pH稳态中发挥基础性作用，并参与调控多种生理和病理过程，如巨胞饮、自噬、细胞侵袭和细胞死亡（包括凋亡、失巢凋亡、碱亡、铁死亡和溶酶体依赖性细胞死亡）。除参与胚胎发育外，V型ATP酶通路功能异常时还会引发神经退行性疾病、骨硬化症、远端肾小管酸中毒和癌症等人类疾病。本文综述了V型ATP酶各亚基异构体的结构与调控机制，并探讨其在癌症生物学和细胞死亡中具有情境依赖性的作用。对V型ATP酶的前沿认知可能为新型抗癌药物或策略的设计提供思路。

原文链接：

The V-ATPases in cancer and cell death