title: Metabolic regulation by HMGB1-mediated autophagy and mitophagy.
abstract: Autophagy is a dynamic process for degradation of cytosolic components such as dysfunctional organelles and proteins and a means for generating metabolic substrates during periods of starvation. Mitochondrial autophagy ("mitophagy") is a selective form of autophagy, which is important in maintaining mitochondrial homeostasis. High mobility group box 1 (HMGB1) plays important intranuclear, cytosolic and extracellular roles in the regulation of autophagy. Cytoplasmic HMGB1 is a novel Beclin 1-binding protein active in autophagy. Extracellular HMGB1 induces autophagy, and this role is dependent on its redox state and receptor (Receptor for Advanced Glycation End products, RAGE) expression. Nuclear HMGB1 modulates the expression of heat shock protein β-1 (HSPB1/HSP27). As a cytoskeleton regulator, HSPB1 is critical for dynamic intracellular trafficking during autophagy and mitophagy. Loss of either HMGB1 or HSPB1 results in a phenotypically similar deficiency in mitophagy typified by mitochondrial fragmentation with decreased aerobic respiration and adenosine triphosphate (ATP) production. These findings reveal a novel pathway coupling autophagy and cellular energy metabolism.
authors.affiliation: The DAMP Laboratory, Department of Surgery, Hillman Cancer Center, University of Pittsburgh Cancer Institute, University of Pittsburgh, PA, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Kang
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Livesey
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Zeh
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lotze
authors.forename: Daolin
authors.initials: D
authors.lastname: Tang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D005786:Gene Expression Regulation; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000473:pathology*; D008954:Models, Biological; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism*; D011485:Protein Binding; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000255:Adenosine Triphosphate; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein