Autophagy is an evolutionarily-conserved catabolic process that degrades cytoplasmic material in the lysosome via a complicated pathway. Functional autophagic pathways are crucial for embryonic development, tissue differentiation, and cell survival. In contrast, the dysregulation of autophagy is involved in multiple pathological conditions including inflammation, immunity, metabolism, and death. Accumulating evidence indicates that high-mobility group box 1 (HMGB1), the best-characterized nonhistone chromosomal protein, and damage-associated molecular pattern molecule can regulate autophagy in a localization-dependent manner. Nuclear HMGB1 regulates heat shock protein β-1 expression to control mitochondrial quality by mitophagy. Cytoplasmic HMGB1 acts as a Belcin-1-binding protein to induce autophagosome formation. Extracellular HMGB1 can bind the receptor for advanced glycation endproducts to induce class III phosphatidylinositol 3-kinase core complex formation in autophagy. In addition, transcriptional and posttranslational regulation of HMGB1 by miRNA34A, miRNA22, miR-let-7f-1, and poly-ADP-ribosylation can fine-tune HMGB1-mediated autophagy. Knockout of HMGB1 in vitro and in vivo limits autophagy that contributes to infection and sterile inflammation. This chapter focuses on the structure and function of HMGB1 as an important regulator of autophagy, as well as its role in cancer therapy, inflammation, immunity, and the central nervous system.
|Original language||English (US)|
|Title of host publication||Autophagy|
|Subtitle of host publication||Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging Volume 8- Human Diseases|
|Number of pages||13|
|State||Published - Jan 1 2016|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)