Calcium cell death regulation

Once apoptosis is triggered, a stereotyped sequence of premitochondrial events occurs that executes the cell death process. In many cases proteins and/or lipid mediators that induce changes in mitochondrial membrane permeability and calcium regulation are produced or activated. For example, the pro-apoptotic Bcl-2 family members Bax, Bad and Bid may associate with the mitochondrial membrane and modify its permeability. Membrane-derived lipid mediators such as ceramide and 4-hydroxynonenal can also induce mitochondrial membrane alterations that are critical for the execution of apoptosis. 

As the power house of the cell, the mitochondrion is essential for energy metabolism. As the motor of cell death (1), this organelle is central to the initiation and regulation of apoptosis. In addition, mitochondria are critically involved in the modulation of intracellular calcium concentration and the mitochondrial respiratory chain is the major source of damaging reactive oxygen species. Mitochondria also play a crucial role in numerous catabolic and anabolic cellular pathways. 

Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death the calcium-apoptosis link. Nat Rev Mol Cell Biol 4 552-565. 

Sustained cytosolic Ca2+ overload usually results in a different route leading to cell death. It mainly relies on the activation of the calcium/calmodulin (CaM)-dependent phosphatase, calcineurin. Calcineurin-catalyzed dephosphorylation promotes apoptosis by regulating the activity of a number of downstream targets, including the pro-apoptotic Bcl-2 family member, Bad (Wang, et al., 1999), and transcription factors of the NFAT (nuclear factor of activated T cells) family (Rao, et al., 1997). There are also other Ca2+-dependent enzymes contributing to the apoptotic events, and they include several DNA-degrading endonucleases (Robertson, et al., 2000) and Ca2+-activated cystein proteases of the calpain family essential for the enzymatic activation of the crucial pro-apoptotic effectors (Altznauer, et al., 2004). 

The expression of genes involved in cell proliferation and cell death is regulated by nuclear transcriptional factors. NFAT (Nuclear Factor of Activated T cells) proteins are a family of Ca2+-dependent transcription factors (Crabtree, 2001), whose nuclear translocation and transcriptional activity is regulated by Ca2+/calmodulin-dependent protein phosphatase, calcineurin (Crabtree, 2001). Thus, NFAT proteins can potentially be activated by diverse stimuli that lead to increased intracellular calcium levels. The NF-kB (nuclear factor kappa B) family... 

Calcium is a unique cation in living systems because of it dominant role in intracellular signaling. Therefore bone cells which must handle massive amounts of this mineral take special care in its regulation. Sustained elevation of intracellular calcium leads to cell death that is not effectively opposed by the usual regulators of apoptosis. We have undertaken to present what is known about how bone cells deal with calcium. However much remains to be learned and the acquisition of this knowledge will inform our treatment of many important medical conditions. 

The importance of calcium in the regulation of skin barrier homeostasis is apparent as calcium is involved in the regeneration process of skin barrier components.4 Hence, the balance of calcium level in skin is closely related to hydration of the skin. Apart from the skin, this ion plays a crucial role in various processes in the body, including the growth, death, differentiation, and function of immune cells. The role of calcium in skin is found to be more complex than previously assumed. The elucidation of calcium regulation mechanism in skin could be useful to understand and solve skin problems. 

Mitochondria are the well-characterized intracellular organelles needed for the production of ATP for all cellular processes. They also play a major role in the regulation of calcium flux and redox state. Moreover, since the mid-1990s, mitochondria have been considered as central effectors for the regulation of cell apoptosis [79]. Apoptosis is a cell death characterized by a number of distinctive... 

---