Objective BI-1 is an anti-apoptotic integral membrane protein located primarily in the intracellular membranes of the endoplasmic reticulum. It over expression promotes autophagy. BI-1 reduces mitochondrial adenosine triphosphate (ATP) levels, which stimulate autophagy. Methods The experiment was performed in cell line and animal models. We used primary BI-1+/+ and BI-1-/- mouse embryonice fibroblast cell (MEF cell).GFP-LC3 transgenic mice were obtained from RIKEN bio resource center Japan. The experiment done in cell line and mice are western blot analysis, electron microscopy, mitochondrial ATP measurement, Immunohistochemistry, real time PCR, Mitochondrial complex assembly analysis. Results Autophagy is a process for delivering cytoplasmic material and organelles to lysosomes for degradation that protects cells during stress responses. Bax inhibitor-1 (BI-1) is an endoplasmic reticulum (ER) membrane protein that protects cells against ER stress and apoptosis. However, the function of BI-1 to modulate autophagy is still controversial. We showed BI-1 over expression promotes autophagy, increasing LC3-II conversion and p62 degradation. BI-1-deficient mice and BI-1 knockout MEF cells have reduced autophagy. Moreover, BI-1 reduced mitochondria ATP levels, increasing AMPK activation, suppressing mTORC1 and stimulating autophagy. Conclusion BI-1 promotes autophagy which contributes to cell survival, presumably in order to compensate for the impairment in mitochondria respiration.