Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 26, Cologne, Germany.
Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann-Strasse 26, Cologne, Germany.
Cell Calcium. 2023 Sep;114:102778. doi: 10.1016/j.ceca.2023.102778. Epub 2023 Jun 19.
Regulation of proliferation and cell death is fundamental for organismal development and for restoring tissue homeostasis after biological stress. During the last years, several forms of regulated cell death have been discovered that share the loss of plasma membrane integrity as a common hallmark and that are collectively known as regulated necrosis (RN) pathways. During RN, plasma membrane damage is sensed by the cell by increases in the levels of intracellular calcium. Interestingly, cytosolic calcium influx can either lead to cell death or survival, given the versatile role of this ion in regulating multiple signaling processes. Among them, membrane repair enables the cells to tolerate the injury and, even in some conditions, survive. Here, we review calcium signaling in the context of RN pathways, with a focus on ferroptosis, a type of RN in which plasma membrane damage is elicited by the accumulation of oxidized lipids. In contrast, other forms of RN such as necroptosis and pyroptosis require dedicated pore-forming proteins for plasma membrane damage and cell death. We first focus on the current knowledge regarding the contribution of calcium to ferroptosis, and then illustrate the similarities and differences in calcium signaling with necroptosis and pyroptosis. Calcium signaling emerges as a key event in the cellular responses to membrane damage and in the regulation of cell death.
细胞增殖和死亡的调控对于机体发育以及生物应激后组织内稳态的恢复至关重要。在过去的几年中，人们发现了几种形式的受调控的细胞死亡，它们都以细胞膜完整性丧失为共同特征，统称为受调控的细胞坏死（RN）途径。在 RN 过程中，细胞通过细胞内钙离子水平的升高来感知细胞膜损伤。有趣的是，由于钙离子在调节多种信号过程中的多功能作用，细胞质钙离子内流既可以导致细胞死亡，也可以导致细胞存活。在这里，我们综述了钙信号在 RN 途径中的作用，重点介绍了铁死亡，这是一种由氧化脂质积累引起的 RN 形式。相比之下，其他形式的 RN，如坏死性凋亡和细胞焦亡，则需要专门的形成孔蛋白来破坏质膜并导致细胞死亡。我们首先关注钙对铁死亡的贡献的最新知识，然后说明钙信号与坏死性凋亡和细胞焦亡的相似性和差异性。钙信号在细胞对膜损伤的反应和细胞死亡的调控中是一个关键事件。
