title: The ancient cell death suppressor BAX inhibitor-1.
abstract: Bax inhibitor-1 (BI-1) was initially identified for its ability to inhibit BAX-induced apoptosis in yeast cells and is the founding member of a family of highly hydrophobic proteins localized in diverse cellular membranes. It is evolutionarily conserved and orthologues from plants can substitute for mammalian BI-1 in regard to its anti-apoptotic function suggesting a high degree of functional conservation. BI-1 interacts with BCL-2 and BCL-XL and, similar to these two anti-apoptotic proteins, the effect of BI-1 on cell death involves changes in the amount of Ca(2+) releasable from intracellular stores. However, BI-1 is also a negative regulator of the endoplasmic reticulum stress sensor IRE1 α, it interacts with G-actin and increases actin polymerization, enhances cancer metastasis by altering glucose metabolism and activating the sodium-hydrogen exchanger, and reduces the production of reactive oxygen species through direct interaction with NADPH-P450 reductase. In this contribution, we summarize what is known about the expression, intracellular localization and structure of BI-1 and specifically illuminate its effects on the intracellular Ca(2+) homeostasis and how this might relate to its other functions. We also present a thorough phylogenetic analysis of BI-1 proteins from major phyla together with paralogues from all BI-1 family members.
authors.affiliation: Neurologische Klinik, Universitätsklinikum Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Henke
authors.forename: Dmitrij A
authors.initials: DA
authors.lastname: Lisak
authors.forename: Lars
authors.initials: L
authors.lastname: Schneider
authors.forename: Jörn
authors.initials: J
authors.lastname: Habicht
authors.forename: Matthias
authors.initials: M
authors.lastname: Pergande
authors.forename: Axel
authors.initials: A
authors.lastname: Methner
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death; D004722:Endoribonucleases / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008322:Mammals; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000199:Actins; D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C484209:TMBIM6 protein, human; D051020:bcl-X Protein; D009251:NADPH-Ferrihemoprotein Reductase; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases; D002118:Calcium