Generation and bioenergetic analysis of cybrids containing mitochondrial DNA from mouse skeletal muscle during aging.
Generation and bioenergetic analysis of cybrids containing mitochondrial DNA from mouse skeletal muscle during aging.
复制标题
衰老过程中含有小鼠骨骼肌线粒体 DNA 的细胞杂种的生成和生物能分析。
DOI：
10.1093/nar/gkp1162
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发表时间：
2010
影响因子：
14.9
通讯作者：
Bai,Yidong
中科院分区：
文献类型：
--
作者：
Li,Youfen;Li,Hong-Zhi;Hu,Peiqing;Deng,Janice;Banoei,MohammadMehdi;Sharma,LokendraKumar;Bai,Yidong
线粒体呼吸链缺陷与各种疾病和正常衰老有关，特别是在包括骨骼肌在内的高能量需求组织中。据报道，肌肉特异性线粒体DNA（mtDNA）突变也会随着衰老而积累。我们对介导线粒体基因表达改变的分子过程的理解与肌肉中mtDNA突变相关的功能障碍将大大增强我们将肌肉mtDNA转移到已建立的细胞系的能力。在这里，我们报告了携带骨骼肌mtDNA的小鼠胞质杂交体的成功产生。使用这种新的方法，我们进行了生物能量分析的细胞轴承mtDNA来自年轻和老年小鼠骨骼肌。携带老年小鼠骨骼肌mtDNA的胞质杂交体的氧化磷酸化偶联和调节能力显著降低。我们的研究结果还显示，与来自老年小鼠肌肉的mtDNA相关的生长能力和细胞活力下降。这些发现表明，在衰老过程中，与受损的mtDNA质量相关的线粒体功能下降导致氧化磷酸化的能力和调节降低。
Mitochondrial respiratory chain defects have been associated with various diseases and normal aging, particularly in tissues with high energy demands including skeletal muscle. Muscle-specific mitochondrial DNA (mtDNA) mutations have also been reported to accumulate with aging. Our understanding of the molecular processes mediating altered mitochondrial gene expression to dysfunction associated with mtDNA mutations in muscle would be greatly enhanced by our ability to transfer muscle mtDNA to established cell lines. Here, we report the successful generation of mouse cybrids carrying skeletal muscle mtDNA. Using this novel approach, we performed bioenergetic analysis of cells bearing mtDNA derived from young and old mouse skeletal muscles. A significant decrease in oxidative phosphorylation coupling and regulation capacity has been observed with cybrids carrying mtDNA from skeletal muscle of old mice. Our results also revealed decrease growth capacity and cell viability associated with the mtDNA derived from muscle of old mice. These findings indicate that a decline in mitochondrial function associated with compromised mtDNA quality during aging leads to a decrease in both the capacity and regulation of oxidative phosphorylation.