Autophagy is an evolutionarily conserved stress response that promotes the lysosomal degradation of intracellular components. The bone marrow stromal cell-derived growth inhibitor (BDGI) functions as a stress sensor which is upregulated by oxidative stress and DNA damage. However, the role of BDGI in autophagic response to certain stresses remains unknown. Here, our results demonstrate that BDGI defines the impact of autophagy induction under stresses. Overexpression of BDGI promotes, while knockdown of BDGI impairs, autophagy. Mechanistically, BDGI localizes to the nucleus and interacts with the transcription factor transcription factor EB to increase the expression of multiple autophagy- and lysosome-related genes. In addition, BDGI regulates autophagy in a p53-dependent manner. Furthermore, BDGI-induced autophagy enables cell survival under stress conditions. Taken together, our study demonstrates that BDGI is a stress sensor that positively regulates autophagy.
Keywords: BDGI; TFEB; autophagy; cell death; p53.
© 2020 Federation of European Biochemical Societies.