LAUSR

In mammals, the Bax inhibitor (TMBIM) family of proteins has cytoprotective properties that are most evident in paradigms of endoplasmic reticulum (ER) stress. The canonical gene of the family called BI-1 has been linked to several human cancers. The crystal structure of a prokaryotic member of the family, BsYetJ, has revealed that the Bax inhibitor proteins are pH sensitive calcium leaks. Our published studies have shown that the yeast Bax Inhibitor, Bxi1p, is localized to the endoplasmic reticulum and is involved in the unfolded protein response (UPR) that is triggered by endoplasmic reticulum (ER) stress. We now show that cells lacking BXI1 have an altered redox microenvironment in the ER: The ER of Δbxi1 cells exposed to dithiothreitol (DTT) and tunicamycin, two drugs known to induce the unfolded protein response (UPR), become more reduced than their wildtype counterparts. Moreover, we also report that cells lacking BXI1 accumulate more calcium in the ER than wildtype cells. Together, our data suggests that Bxi1p is involved in regulating the ER microenvironment. Other members of the TMBIM family may have the same role in normal and cancer cells. [Our laboratory is supported by grant NIGMS R15 GM110578, awarded to N. Austriaco.] Note: This abstract was not presented at the meeting. Citation Format: David Eagan, Joseph Alisch, Liam McDonough, Savannah Benko, Walter Jacob, Lukas Ritzer, James Mullin, John O9Reilly, Nicanor Austriaco. Yeast Bax Inhibitor (BXI1) is involved in redox and calcium homeostasis of the ER in S. cerevisiae [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5472. doi:10.1158/1538-7445.AM2017-5472