High-Mobility Group Box 1 and Autophagy

High-mobility group box 1 (HMGB1) is an architectural chromosomal protein and stress sensor that plays a critical role in various physiological and pathological processes, including cell death and survival.Autophagy is the major pathway involved in the degradation of proteins and organelles, maintenance of cellular homeostasis, and promotion of survival during environmental stress.HMGB1 plays an important location-dependent role in the regulation of autophagy.Nuclear HMGB1 contributes to mitophagy by regulation of heat shock protein beta-1 (HSPB1) expression and cytoskeleton dynamics.Cytoplasmic HMGB1 is a novel coiled-coil myosin-like BCL2-interacting protein (BECN1)-binding protein in the induction of autophagosome formation.Extracellular-reduced HMGB1 triggers autophagy in an advanced glycosylation end product-specific receptor (AGER)-dependent manner.HMGB1-dependent autophagy promotes chemotherapy resistance, sustains the tumor metabolism requirement and T-cell survival, prevents polyglutamine aggregates and excitotoxicity, and protects against endotoxemia, bacterial infection, and ischemiareperfusion injury in vitro or in animal studies.Targeting the HMGB1-mediated autophagy pathway may be required to address whether or not this approach is therapeutically advantageous in human disease.