J Cell Sci. 2018 Jan 11. pii: jcs.211201. doi: 10.1242/jcs.211201. [Epub ahead of print]
Inflachromene inhibits autophagy through modulation of Beclin 1 activity.
Kim YH1,2, Kwak MS1, Shin JM1,2, Hayuningtyas RA1,2, Choi JE3, Shin JS4,2,5.
1Department of Microbiology, Yonsei University College of Medicine, Seoul 03722, South Korea.2Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, South Korea.3Department of Pediatrics, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul 07061, South Korea firstname.lastname@example.org email@example.comDepartment of Microbiology, Yonsei University College of Medicine, Seoul 03722, South Korea firstname.lastname@example.org email@example.comSeverance Biomedical Science Institute and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, South Korea.
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 ubiquitination 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.