Nature Genetics
- 38, 1261 - 1268 (2006)
Published online: 1 October 2006; | doi:10.1038/ng1897
Differences in reactive oxygen species production explain the phenotypes associated with common mouse mitochondrial DNA variantsRaquel Moreno-Loshuertos1, Rebeca Acín-Pérez1, Patricio Fernández-Silva1, Nieves Movilla1, Acisclo Pérez-Martos1, Santiago Rodriguez de Cordoba2, M Esther Gallardo2 & José Antonio Enríquez11
Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Miguel Servet 177, Zaragoza 50013, Spain. 2
Departamento de Inmunología, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Avda Ramiro de Maeztu 9, Madrid 28040, Spain.
Correspondence should be addressed to José Antonio Enríquez enriquez@unizar.es 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.
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