Calcium and cell death mechanisms: A perspective from the cell death community

Research during the past several decades has provided convincing evidence for a crucial role of the Ca2+ ion in cell signaling. Hence, intracellular Ca2+ transients have been implicated in most aspects of cell physiology, including gene transcription, cell cycle regulation and cell proliferation. Further, the Ca2+ ion has been found to also play an important role in cell death regulation. Thus, necrotic cell death was early associated with intracellular Ca2+ overload, and multiple functions in the apoptotic process have subsequently been found to be governed by Ca2+ signaling. More recently, other modes of cell death, notably anoikis and autophagic cell death, have been demonstrated to also be modulated by Ca2+ transients. Characteristics, interrelationship and mechanisms involved in Ca2+ regulation of these cell death modalities are discussed in this review.