Ca2+ signaling and cell death

• Published in: Cell calcium (Edinburgh) 2023-07, Vol.113, p.102759-102759, Article 102759
• Main Authors: Dhaouadi, Nada, Vitto, Veronica Angela Maria, Pinton, Paolo, Galluzzi, Lorenzo, Marchi, Saverio
• Format: Article
• Language: English
• Subjects: Apoptosis; Bcl2; Endoplasmic reticulum, immunogenic cell death; Lysosomes; MPT-driven necrosis
• ISSN: 0143-4160; 1532-1991
• DOI: 10.1016/j.ceca.2023.102759

•Virtually all regulated cell death variants can be influenced by intracellular Ca2+ fluxes.•Intracellular Ca2+ overload constitutes a major perturbation of intracellular homeostasis that affects a variety of organelles and potentially culminates with cell death.•Multiple factors dictate cellular responses to Ca2+ fluxes, including the nature of Ca2+-mobilizing agents, the Ca2+ handling machinery, and the microenvironmental Ca2+ levels and kinetics. 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. [Display omitted]