High mobility group box 1 (HMGB1) is named for its electrophoretic mobility on polyacrylamide gels when it was first identified in calf thymus in 1973. HMGB1 plays a critical role in the stress response not only inside the cell as a DNA chaperone and cell death regulator, but also outside the cell as the prototypic damage-associated molecular pattern molecule. The physiological and pathological role of HMGB1 in health and disease has been widely studied for years. In this chapter, we will focus on the release and function of HMGB1 in cell death types such as apoptosis, autophagy, and necrosis.
Part of the book: Cell Death
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 ischemia-reperfusion 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.
Part of the book: Autophagy in Current Trends in Cellular Physiology and Pathology