Inflachromene inhibits autophagy through modulation of Beclin 1 activity.

ABSTRACT

Autophagy is a central intracellular catabolic mechanism that mediates the degradation of cytoplasmic proteins and organelles, and regulation of autophagy is essential for homeostasis. HMGB1 is an important sepsis mediator when secreted and also functions as an inducer of autophagy by binding to Beclin 1. In this study, we studied the effect of inflachromene (ICM), a novel HMGB1 secretion inhibitor, on autophagy. ICM inhibited autophagy by inhibiting nucleocytoplasmic translocation of HMGB1 and by increasing Beclin 1 ubiquitylation for degradation by enhancing the interaction between Beclin 1 and E3 ubiquitin ligase RNF216. These data suggest that ICM could be used as a potential autophagy suppressor.