Division of Molecular & Clinical Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, United Kingdom.
Cell Calcium. 2018 Jan;69:28-36. doi: 10.1016/j.ceca.2017.06.001. Epub 2017 Jun 8.
The plasma membrane Ca-ATPase (PMCA) is a ubiquitously expressed, ATP-driven Ca pump that is critical for maintaining low resting cytosolic Ca ([Ca]) in all eukaryotic cells. Since cytotoxic Ca overload has such a central role in cell death, the PMCA represents an essential "linchpin" for the delicate balance between cell survival and cell death. In general, impaired PMCA activity and reduced PMCA expression leads to cytotoxic Ca overload and Ca dependent cell death, both apoptosis and necrosis, whereas maintenance of PMCA activity or PMCA overexpression is generally accepted as being cytoprotective. However, the PMCA has a paradoxical role in cell death depending on the cell type and cellular context. The PMCA can be differentially regulated by Ca-dependent proteolysis, can be maintained by a localised glycolytic ATP supply, even in the face of global ATP depletion, and can be profoundly affected by the specific phospholipid environment that it sits within the membrane. The major focus of this review is to highlight some of the controversies surrounding the paradoxical role of the PMCA in cell death and survival, challenging the conventional view of ATP-dependent regulation of the PMCA and how this might influence cell fate.
质膜 Ca2+-ATP 酶（PMCA）是一种普遍表达的、ATP 驱动的 Ca2+泵，对所有真核细胞维持低静息细胞浆 Ca2+([Ca2+])浓度至关重要。由于细胞毒性 Ca2+过载在细胞死亡中起着如此核心的作用，PMCA 代表了细胞存活和细胞死亡之间微妙平衡的重要“关键”。一般来说，PMCA 活性受损和 PMCA 表达减少会导致细胞毒性 Ca2+过载和 Ca2+依赖性细胞死亡，包括凋亡和坏死，而维持 PMCA 活性或 PMCA 过表达通常被认为具有细胞保护作用。然而，PMCA 在细胞死亡中的作用具有矛盾性，这取决于细胞类型和细胞环境。PMCA 可以通过 Ca2+依赖性蛋白水解进行差异调节，可以通过局部糖酵解 ATP 供应来维持，即使在全球 ATP 耗竭的情况下也是如此，并且可以受到其在膜内所处的特定磷脂环境的深刻影响。本综述的主要重点是强调 PMCA 在细胞死亡和存活中的矛盾作用所围绕的一些争议，挑战了 PMCA 的 ATP 依赖性调节的传统观点，以及这可能如何影响细胞命运。
