title: High-mobility group box 1 is dispensable for autophagy, mitochondrial quality control, and organ function in vivo.
abstract: In vitro studies have demonstrated a critical role for high-mobility group box 1 (HMGB1) in autophagy and the autophagic clearance of dysfunctional mitochondria, resulting in severe mitochondrial fragmentation and profound disturbances of mitochondrial respiration in HMGB1-deficient cells. Here, we investigated the effects of HMGB1 deficiency on autophagy and mitochondrial function in vivo, using conditional Hmgb1 ablation in the liver and heart. Unexpectedly, deletion of Hmgb1 in hepatocytes or cardiomyocytes, two cell types with abundant mitochondria, did not alter mitochondrial structure or function, organ function, or long-term survival. Moreover, hepatic autophagy and mitophagy occurred normally in the absence of Hmgb1, and absence of Hmgb1 did not significantly affect baseline and glucocorticoid-induced hepatic gene expression. Collectively, our findings suggest that HMGB1 is dispensable for autophagy, mitochondrial quality control, the regulation of gene expression, and organ function in the adult organism.
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Huebener
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA; Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
authors.forename: Geum-Youn
authors.initials: GY
authors.lastname: Gwak
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Pradere
authors.affiliation: Department of Neurology, Columbia University, New York, NY 10032, USA.
authors.forename: Catarina M
authors.initials: CM
authors.lastname: Quinzii
authors.affiliation: Herbert Irving Comprehensive Cancer Center and Department of Biomedical Informatics, Columbia University, New York, NY 10032, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Friedman
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
authors.forename: Chyuan-Sheng
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Division of Preventive Medicine and Nutrition, Department of Medicine, Columbia University, New York, NY 10032, USA; Institute of Human Nutrition, Columbia University, New York, NY 10032, USA.
authors.forename: Chad M
authors.initials: CM
authors.lastname: Trent
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Mederacke
authors.affiliation: Department of Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Enpeng
authors.initials: E
authors.lastname: Zhao
authors.affiliation: Institute of Human Nutrition, Columbia University, New York, NY 10032, USA.
authors.forename: Dianne H
authors.initials: DH
authors.lastname: Dapito
authors.affiliation: Institute of Human Nutrition, Columbia University, New York, NY 10032, USA.
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Division of Preventive Medicine and Nutrition, Department of Medicine, Columbia University, New York, NY 10032, USA; Institute of Human Nutrition, Columbia University, New York, NY 10032, USA.
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
authors.affiliation: Department of Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Czaja
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA; Institute of Human Nutrition, Columbia University, New York, NY 10032, USA. Electronic address: rfs2102@cumc.columbia.edu.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Schwabe
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D001786:Blood Glucose / Q000378:metabolism; D004734:Energy Metabolism; D015870:Gene Expression; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D010085:Oxidative Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D012333:RNA, Messenger; D000255:Adenosine Triphosphate