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.