Differences in reactive oxygen species production explain the phenotypes associated with common mouse mitochondrial DNA variants
Differences in reactive oxygen species production explain the phenotypes associated with common mouse mitochondrial DNA variants
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DOI：
10.1038/ng1897
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发表时间：
2006-11-01
期刊：
影响因子：
30.8
通讯作者：
Enriquez, Jose Antonio
中科院分区：
文献类型：
--
作者：
Moreno-Loshuertos, Raquel;Acin-Perez, Rebeca;Enriquez, Jose Antonio
人类和小鼠中常见的线粒体DNA（mtDNA）单倍型与各种表型相关，包括学习表现和疾病易感性。值得注意的是，mtDNA单倍型对细胞呼吸没有影响。在这里，我们使用在相同核背景下携带四种不同常见小鼠线粒体DNA单倍型的细胞系，表明细胞系之间相似的呼吸水平只是明显的，并且是由活性氧簇的不同产生触发的补偿机制的结果。我们观察到，NIH 3 T3或NZB mtDNA的细胞的每分子mtDNA的呼吸能力低于C57 BL/6 J、CBA/J或BALB/cJ mtDNA的细胞。此外，我们还确定了这些差异背后的遗传因素。我们的数据提供了深入了解与常见mtDNA变异相关的复杂表型的分子基础，并预测mtDNA单核苷酸多态性对人类表型变异的相关贡献。
Common mitochondrial DNA (mtDNA) haplotypes in humans and mice have been associated with various phenotypes, including learning performance and disease penetrance. Notably, no influence of mtDNA haplotype in cell respiration has been demonstrated. Here, using cell lines carrying four different common mouse mtDNA haplotypes in an identical nuclear background, we show that the similar level of respiration among the cell lines is only apparent and is a consequence of compensatory mechanisms triggered by different production of reactive oxygen species. We observe that the respiration capacity per molecule of mtDNA in cells with the NIH3T3 or NZB mtDNA is lower than in those with the C57BL/6J, CBA/J or BALB/cJ mtDNA. In addition, we have determined the genetic element underlying these differences. Our data provide insight into the molecular basis of the complex phenotypes associated with common mtDNA variants and anticipate a relevant contribution of mtDNA single nucleotide polymorphisms to phenotypic variability in humans.