Institute of Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University School of Life Science and Technology, Xi'an 710049, China.
J Cell Biochem. 2013 Jan;114(1):212-9. doi: 10.1002/jcb.24356.
Mitochondrial dynamics maintains normal mitochondrial function by degrading damaged mitochondria and generating newborn mitochondria. The accumulation of damaged mitochondria influences the intracellular environment by promoting mitochondrial dysfunction, and thus initiating a vicious cycle. Oxidative stress induces mitochondrial malfunction, which is involved in many cardiovascular diseases. However, the mechanism of mitochondrial accumulation in cardiac myoblasts remains unclear. We observed mitochondrial dysfunction and an increase in mitochondrial mass under the oxidative conditions produced by tert-butyl hydroperoxide (tBHP) in cardiac myoblast H9c2 cells. However, in contrast to the increase in mitochondrial mass, mitochondrial DNA (mtDNA) decreased, suggesting that enhanced mitochondrial biogenesis may be not the primary cause of the mitochondrial accumulation. Therefore, we investigated changes in a number of proteins involved in autophagy. Beclin1, Atg12-Atg5 conjugate, Atg7 contents decreased but LC3-II accumulated in tBHP-treated H9c2 cells. Moreover, the capacity for acid hydrolysis decreased in H9c2 cells. We also demonstrated a decrease in DJ-1 protein under the oxidative conditions that deregulate mitochondrial dynamics. These results reveal that autophagy became defective under oxidative stress. We therefore suggest that defects in autophagy mediate mitochondrial accumulation under these conditions.
线粒体动力学通过降解受损的线粒体和产生新生的线粒体来维持正常的线粒体功能。受损线粒体的积累通过促进线粒体功能障碍影响细胞内环境，从而引发恶性循环。氧化应激诱导线粒体功能障碍，这与许多心血管疾病有关。然而，心肌细胞中线粒体积累的机制尚不清楚。我们观察到在心肌细胞 H9c2 中由叔丁基过氧化物（tBHP）产生的氧化条件下存在线粒体功能障碍和线粒体质量增加。然而，与线粒体质量的增加相反，线粒体 DNA（mtDNA）减少，这表明增强的线粒体生物发生可能不是线粒体积累的主要原因。因此，我们研究了参与自噬的多种蛋白质的变化。Beclin1、Atg12-Atg5 缀合物和 Atg7 的含量减少，但 tBHP 处理的 H9c2 细胞中 LC3-II 积累。此外，H9c2 细胞中的酸水解能力下降。我们还证明了在氧化条件下 DJ-1 蛋白减少，这会导致线粒体动力学失调。这些结果表明自噬在氧化应激下出现缺陷。因此，我们认为自噬缺陷介导了这些条件下的线粒体积累。
