Format

Send to

Choose Destination
Cell Metab. 2014 Mar 4;19(3):539-47. doi: 10.1016/j.cmet.2014.01.014.

High-mobility group box 1 is dispensable for autophagy, mitochondrial quality control, and organ function in vivo.

Author information

1
Department of Medicine, Columbia University, New York, NY 10032, USA.
2
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.
3
Department of Neurology, Columbia University, New York, NY 10032, USA.
4
Herbert Irving Comprehensive Cancer Center and Department of Biomedical Informatics, Columbia University, New York, NY 10032, USA.
5
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
6
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.
7
Department of Medicine, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
8
Institute of Human Nutrition, Columbia University, New York, NY 10032, USA.
9
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.

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.

PMID:
24606906
PMCID:
PMC4099361
DOI:
10.1016/j.cmet.2014.01.014
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center