Metabolic regulation of the PMCA: Role in cell death and survival.
Metabolic regulation of the PMCA: Role in cell death and survival.
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DOI：
10.1016/j.ceca.2017.06.001
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发表时间：
2018-01
期刊：
影响因子：
4
通讯作者：
Bruce JIE
中科院分区：
文献类型：
--
作者：
Bruce JIE
PMCA是ATP驱动的Ca 2+泵，对于维持低细胞溶质钙至关重要。PMCA在细胞死亡和存活中具有重要但矛盾的作用。PMCA可以通过半胱天冬酶/钙蛋白酶切割进行差异调节。在代谢应激期间，糖酵解ATP的供应可能足以为PMCA提供能量。PMCA的ATP敏感性可通过酸性磷脂调节。质膜Ca ~（2+）-ATP酶（PMCA）是一种广泛表达的ATP驱动的Ca ~（2+）泵，对维持所有真核细胞中低静息胞浆Ca ~（2+）（[Ca ~（2+）]i）至关重要。由于细胞毒性Ca 2+超载在细胞死亡中具有如此重要的作用，PMCA代表了细胞存活和细胞死亡之间微妙平衡的重要“关键”。通常，受损的PMCA活性和降低的PMCA表达导致细胞毒性Ca 2+过载和Ca 2+依赖性细胞死亡，包括凋亡和坏死，而维持PMCA活性或PMCA过表达通常被认为是细胞保护性的。然而，PMCA在细胞死亡中具有矛盾的作用，这取决于细胞类型和细胞环境。PMCA可以通过Ca 2+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，即使在面临全球ATP耗竭的情况下也是如此，并且可以受到其位于膜内的特定磷脂环境的深刻影响。本次审查的主要重点是突出一些争议周围的矛盾作用的PMCA在细胞死亡和生存，挑战传统的观点ATP依赖性调节的PMCA，这可能会影响细胞的命运。
The PMCA is an ATP-driven Ca2+ pump critical for the maintenance of low cytosolic calcium. The PMCA has an important but paradoxical role in cell death and survival. The PMCA can be differentially regulated by caspase/calpain cleavage. Glycolytic ATP supply may be sufficient to fuel the PMCA during metabolic stress. The ATP sensitivity of the PMCA can be regulated by acidic phospholipids. The plasma membrane Ca2+-ATPase (PMCA) is a ubiquitously expressed, ATP-driven Ca2+ pump that is critical for maintaining low resting cytosolic Ca2+ ([Ca2+]i) in all eukaryotic cells. Since cytotoxic Ca2+ 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 Ca2+ overload and Ca2+ 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 Ca2+-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.
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