LAUSR

Yeast Bax inhibitor-1 (BXI1/YBH3) encodes a protein that belongs to the Bax Inhibitor (TMBIM) family of proteins that all contain a transmembrane BAX inhibitor motif. The crystal structure of a prokaryotic member of the family, BsYetJ, has revealed that the Bax inhibitor proteins are pH sensitive calcium leaks. In mammals, the Bax inhibitor family of proteins has cytoprotective properties that are most evident in paradigms of endoplasmic reticulum (ER) stress. Our published studies have shown that yeast Bxi1p is localized to the endoplasmic reticulum and is involved in the unfolded protein response (UPR) that is triggered by ER stress. BXI1 is thought to act via a mechanism involving altered calcium dynamics. We now show that cells lacking BXI1 accumulate higher levels of calcium in their ER as compared to their wildtype counterparts. We have also over expressed Bxi1p in E.coli and have used a fura-2 based calcium assay to show that the protein facilitates the influx of extracellular calcium into the cell. Our preliminary data with Δbxi1 Δpmr1 double mutants suggest that Bxi1p and Pmr1p, the Golgi-ER calcium pump, function in an antagonistic manner. [Our laboratory is supported by grant NIGMS R15 GM110578, awarded to N. Austriaco.] Citation Format: Nicholas Andrews, Nicholas Mello, Liam McDonough, Joseph Alisch, David Eagan, James Mullin, Alfredo Gonzalez, Nicanor Austriaco. Yeast Bax Inhibitor, BXI1, is involved in calcium homeostasis of the ER in Saccharomyces cerevisiae [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 308.