HMGB1-dependent and -independent autophagy

Abstract

HMGB1 (high mobility group box 1) is a multifunctional, ubiquitous protein located inside and outside cells that plays a critical role in various physiological and pathological processes including cell development, differentiation, inflammation, immunity, metastasis, metabolism, and death. Increasing evidence demonstrates that HMGB1-dependent autophagy promotes chemotherapy resistance, sustains tumor metabolism requirements and T cell survival, prevents polyglutamine aggregates and excitotoxicity, and protects against endotoxemia, bacterial infection, and ischemia-reperfusion injury in vitro or in vivo. In contrast, HMGB1 may not be required for autophagy in some organs such as the liver and heart. Understanding HMGB1-dependent and -independent autophagy in more detail will provide insight into the integrated stress response and guide HMGB1-based therapeutic intervention.

Keywords: HMGB1; autophagy; knockin; knockout; phenotype.

Figure 1. HMGB1 is involved in autophagy and other stress responses. (A) HMGB1 plays important nuclear, cytosolic, and extracellular roles in the regulation of autophagy. (B and C) Various phenotypes of HMGB1 knockout (B) and knockin (C) mice with or without stress (indicated by lightning bolt).