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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 539-547 |
| Number of pages | 9 |
| Journal | Cell Metabolism |
| Volume | 19 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 4 2014 |
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ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Physiology
Cite this
High-Mobility group box 1 is dispensable for autophagy, mitochondrial quality control, and organ function in vivo. / Huebener, Peter; Gwak, Geum Youn; Pradere, Jean Philippe; Quinzii, Catarina M.; Friedman, Richard; Lin, Chyuan Sheng; Trent, Chad M.; Mederacke, Ingmar; Zhao, Enpeng; Dapito, Dianne H.; Lin, Yuxi; Goldberg, Ira J.; Czaja, Mark J.; Schwabe, Robert F.
In: Cell Metabolism, Vol. 19, No. 3, 04.03.2014, p. 539-547.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - High-Mobility group box 1 is dispensable for autophagy, mitochondrial quality control, and organ function in vivo
AU - Huebener, Peter
AU - Gwak, Geum Youn
AU - Pradere, Jean Philippe
AU - Quinzii, Catarina M.
AU - Friedman, Richard
AU - Lin, Chyuan Sheng
AU - Trent, Chad M.
AU - Mederacke, Ingmar
AU - Zhao, Enpeng
AU - Dapito, Dianne H.
AU - Lin, Yuxi
AU - Goldberg, Ira J.
AU - Czaja, Mark J.
AU - Schwabe, Robert F.
PY - 2014/3/4
Y1 - 2014/3/4
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84895754369&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2014.01.014
DO - 10.1016/j.cmet.2014.01.014
M3 - Article
C2 - 24606906
AN - SCOPUS:84895754369
VL - 19
SP - 539
EP - 547
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 3
ER -