TMBIM protein family: ancestral regulators of cell death

Artículo de publicación ISIThe control of apoptosis in mammals has been historically associated with the activity of the BCL-2 family of proteins at the mitochondria. In the past years, a novel group of cell death regulators have emerged, known as the Transmembrane BAX Inhibitor-1 Motif-containing (TMBIM) protein family. This group of proteins is composed of at least six highly conserved members expressed in mammals, with homologs in insects, fish, plants, viruses and yeast. Different studies indicate that all TMBIM family members have inhibitory activities in different setting of apoptosis. Here, we overview and integrate possible mechanisms underlying the impact of the TMBIM protein family in the regulation of cell death, which include activities at diverse subcellular compartments, including death receptor regulation, modulation of endoplasmic reticulum (ER) calcium homeostasis, ER stress signaling, autophagy, reactive oxygen species production, among other effects. The possible intersection between the BCL-2 and TMBIM family in the control of cell death is also discussed, in addition to their implication in the progression of cancer.FONDEF D11l1007, 3130365; Ring Initiative ACT1109; Millennium Institute P09-015-F; Alzheimers Association, FONDECYT 1100176; Muscular Dystrophy Association, ALS Therapy Alliance; FONDECYT 3130365, 1140549; ECOS CONICYT C13S02 CONICYT Grant USA2013-000