Differences in reactive oxygen species production explain the phenotypes associated with common mouse mitochondrial DNA variants.
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.
Moreno-Loshuertos
Raquel
R
Departamento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, Miguel Servet 177, Zaragoza 50013, Spain.
Acín-Pérez
Rebeca
R
Fernández-Silva
Patricio
P
Movilla
Nieves
N
Pérez-Martos
Acisclo
A
Rodriguez de Cordoba
Santiago
S
Gallardo
M Esther
ME
Enríquez
José Antonio
JA
D000220:Adaptation, Biological; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002952:Citric Acid Cycle; D003433:Crosses, Genetic; D004272:DNA, Mitochondrial / Q000032:analysis*; D004622:Embryo, Mammalian; D005690:Galactose / Q000494:pharmacology; D014644:Genetic Variation; D006239:Haplotypes; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D041681:NIH 3T3 Cells; D010641:Phenotype; D011110:Polymorphism, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction
D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D005690:Galactose