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
Department of Medicine, Columbia University, New York, NY 10032, USA.
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.
Cell Metab. 2014 Mar 4;19(3):539-47. doi: 10.1016/j.cmet.2014.01.014.
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.
体外研究表明，高迁移率族蛋白B1（HMGB1）在自噬及功能失调线粒体的自噬清除过程中起关键作用，这会导致HMGB1缺陷细胞中出现严重的线粒体碎片化及线粒体呼吸的显著紊乱。在此，我们利用肝脏和心脏中条件性Hmgb1基因敲除，研究了HMGB1缺陷在体内对自噬和线粒体功能的影响。出乎意料的是，在肝细胞或心肌细胞（两种富含线粒体的细胞类型）中删除Hmgb1，并未改变线粒体结构或功能、器官功能或长期存活率。此外，在缺乏Hmgb1的情况下，肝脏自噬和线粒体自噬正常发生，且缺乏Hmgb1并未显著影响基础及糖皮质激素诱导的肝脏基因表达。总体而言，我们的研究结果表明，在成年生物体中，HMGB1对于自噬、线粒体质量控制、基因表达调控及器官功能而言并非必需。
