Endoplasmic reticulum protein BI-1 regulates Ca2+-mediated bioenergetics to promote autophagy

• DOI: 10.1101/gad.184325.111
• Publication Date: 2012-05-15T17:52:51Z
• Authors: Renata Sano; Ying-Chen Claire Hou; Michael Hedvat; Ricardo G. Correa; Chih-Wen Shu; Maryla Krajewska; Paul W. Diaz; Craig M. Tamble; Giovanni Quarato; Roberta A. Gottlieb; Masaya Yamaguchi; Victor Nizet; Russell Dahl; David D. Thomas; Stephen W. Tait; Douglas R. Green; Paul B. Fisher; Shu-Ichi Matsuzawa; John C. Reed
• Keywords: Bioenergetics

Autophagy is a lysosomal degradation pathway that converts macromolecules into substrates for energy production during nutrient-scarce conditions such as those encountered in tumor microenvironments. Constitutive mitochondrial uptake of endoplasmic reticulum (ER) Ca 2+ mediated by inositol triphosphate receptors (IP 3 Rs) maintains cellular bioenergetics, thus suppressing autophagy. We show the ER membrane protein Bax inhibitor-1 (BI-1) promotes autophagy an IP R-dependent manner. By reducing steady-state levels via Rs, BI-1 influences oxygen consumption, impacting ATP levels, and stimulating Furthermore, BI-1-deficient mice reduced basal autophagy, experimentally expression impairs xenograft growth vivo. BI-1's ability to promote could be dissociated from its known function modulator IRE1 signaling context stress. The results reveal novel regulator bridges between mitochondria, consumption contributing resilience face metabolic