Ca2+ signaling and cell death

: Multiple forms of regulated cell death (RCD) have been characterized, each of which originates from the activation of a dedicated molecular machinery. RCD can occur in purely physiological settings or upon failing cellular adaptation to stress. Ca2+ions have been shown to physically interact with - and hence regulate - various components of the RCD machinery. Moreover, intracellular Ca2+ accumulation can promote organellar dysfunction to degree that can be overtly cytotoxic or sensitize cells to RCD elicited by other stressors. Here, we provide an overview of the main links between Ca2+and different forms of RCD, including apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, lysosome-dependent cell death, and parthanatos.