TMBIM-mediated Ca²⁺ homeostasis and cell death

Ca²⁺ is a ubiquitous intracellular messenger that regulates numerous physiological activities in humans, animals, plants, and bacteria. Cytosolic Ca²⁺ is kept at a low level, but subcellular organelles such as the endoplasmic reticulum (ER) and Golgi apparatus maintain high-concentration Ca²⁺ stores. Under resting conditions, store Ca²⁺ homeostasis is dynamically regulated to equilibrate between active Ca²⁺ uptake and passive Ca²⁺ leak processes. The evolutionarily conserved Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) proteins mediate Ca²⁺ homeostasis and cell death. This review focuses on recent advances in functional and structural analysis of TMBIM proteins in regulation of the two related functions. The roles of TMBIM proteins in pathogen infection and cancer are also discussed with prospects for treatment. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.