BAX Inhibitor-1, an ancient cell death suppressor in animals and plants with prokaryotic relatives

BAX Inhibitor-1 (Bl-1) was originally described as testis enhanced gene transcript in mammals. Functional screening in yeast for human proteins that can inhibit the cell death provoking function of BAX, a proapoptotic Bcl-2 family member, led to functional characterisation and renaming of Bl-1. The identification of functional homologues of Bl-1 in plants and yeast widened the understanding of Bl-1 function as an ancient suppressor of programmed cell death. Bl-1 is one of the few cell death suppressors conserved in animals and plants. Computer predictions and experimental data together suggest that Bl-1 is a membrane spanning protein with 6 to 7 transmembrane domains and a cytoplasmic C-terminus sticking in the endoplasmatic reticulum and nuclear envelope. Proteins similar to Bl-1 are present in other eukaryotes, bacteria, and even viruses encode Bl-1 like proteins. Bl-1 is involved in development, response to biotic and abiotic stress and probably represents an indispensable cell protectant. Bl-1 appears to suppress cell death induced by mitochondrial dysfunction, reactive oxygen species or elevated cytosolic Ca²⁺ levels. This review focuses on the present understanding about Bl-1 and suggests potential directions for further analyses of this increasingly noticed protein.