Nelson N, Klionsky D J
Department of Biochemistry, Tel Aviv University, Ramat Aviv, Israel.
Experientia. 1996 Dec 15;52(12):1101-10. doi: 10.1007/BF01952108.
Vacuolar H(+)-adenosine triphosphatase (V-ATPase) is composed of distinct catalytic (V1) and membrane (V0) sectors containing several subunits. The biochemistry of the enzyme was mainly studied in organelles from mammalian cells such as chromaffin granules and clathrin-coated vesicles. Subsequently, mammalian cDNAs and yeast genes encoding subunits of V-ATPase were cloned and sequenced. The sequence information revealed the relation between V- and F-ATPase that evolved from a common ancestor. The isolation of yeast genes encoding subunits of V-ATPase opened an avenue for molecular biology studies of the enzyme. Because V-ATPase is present in every known eukaryotic cell and provides energy for vital transport systems, it was anticipated that disruption of genes encoding V-ATPase subunits would be lethal. Fortunately, yeast cells can survive the absence of V-ATPase by 'drinking' the acidic medium. So far only yeast cells have been shown to be viable without an active V-ATPase. In contrast to yeast, mammalian cells may have more than one gene encoding each of the subunits of the enzyme. Some of these genes encode tissue- and/or organelle-specific subunits. Expression of these specific cDNAs in yeast cells may reveal their unique functions in mammalian cells. Following the route from mammals to yeast and back may prove useful in the study of many other complicated processes.
液泡H⁺-ATP酶（V-ATP酶）由包含多个亚基的不同催化（V1）和膜（V0）结构域组成。该酶的生物化学主要在哺乳动物细胞的细胞器中进行研究，如嗜铬颗粒和网格蛋白包被小泡。随后，编码V-ATP酶亚基的哺乳动物cDNA和酵母基因被克隆和测序。序列信息揭示了从共同祖先进化而来的V-ATP酶和F-ATP酶之间的关系。编码V-ATP酶亚基的酵母基因的分离为该酶的分子生物学研究开辟了一条途径。由于V-ATP酶存在于每个已知的真核细胞中，并为重要的转运系统提供能量，预计编码V-ATP酶亚基的基因的破坏将是致命的。幸运的是，酵母细胞可以通过“饮用”酸性培养基在没有V-ATP酶的情况下存活。到目前为止，只有酵母细胞被证明在没有活性V-ATP酶的情况下是可行的。与酵母不同，哺乳动物细胞可能有不止一个基因编码该酶的每个亚基。其中一些基因编码组织和/或细胞器特异性亚基。这些特定cDNA在酵母细胞中的表达可能揭示它们在哺乳动物细胞中的独特功能。沿着从哺乳动物到酵母再返回的路线可能在许多其他复杂过程的研究中被证明是有用的。
