Amo Taku, Yadava Nagendra, Oh Richard, Nicholls David G, Brand Martin D
MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB2 0XY, UK.
Gene. 2008 Mar 31;411(1-2):69-76. doi: 10.1016/j.gene.2008.01.007. Epub 2008 Jan 26.
Studies of both survival after sepsis and sperm motility in human populations have shown significant associations with common European mitochondrial DNA haplogroups, and have led to proposals that mitochondria bearing haplogroup H have different bioenergetic capacities than those bearing haplogroup T. However, the validity of such associations assumes that there are no non-random influences of nuclear genes or other factors. Here, we removed the effect of any differences in nuclear genes by constructing transmitochondrial cybrids harbouring mitochondria with either haplogroup H or haplogroup T in cultured A549 human lung carcinoma cells with identical nuclear backgrounds. We compared the bioenergetic capacities and coupling efficiencies of mitochondria isolated from these cells, and of mitochondria retained within the cells, as a critical experimental test of the hypothesis that these haplogroups affect mitochondrial bioenergetics. We found that there were no functionally-important bioenergetic differences between mitochondria bearing these haplogroups, using either isolated mitochondria or mitochondria within cells.
对脓毒症患者生存率和人类精子活力的研究表明,这两者与常见的欧洲线粒体DNA单倍群存在显著关联,并由此提出了带有单倍群H的线粒体与带有单倍群T的线粒体具有不同生物能量能力的观点。然而,此类关联的有效性假定不存在核基因或其他因素的非随机影响。在此,我们通过在具有相同核背景的培养A549人肺癌细胞中构建携带单倍群H或单倍群T线粒体的线粒体杂交细胞,消除了核基因差异的影响。我们比较了从这些细胞中分离出的线粒体以及细胞内保留的线粒体的生物能量能力和偶联效率,以此作为对这些单倍群影响线粒体生物能量学这一假说的关键实验检验。我们发现,无论是分离出的线粒体还是细胞内的线粒体,携带这些单倍群的线粒体在功能上并无重要的生物能量差异。