Human mitochondrial haplogroup H: the highest VO2max consumer--is it a paradox?

Mitochondrial background has been demonstrated to influence maximal oxygen uptake (VO2max, in mLkg−1min−1), but this genetic influence can be compensated for by regular exercise. A positive correlation among electron transport chain (ETC) coupling, ATP and reactive oxygen species (ROS) production has been established, and mitochondrial variants have been reported to show differences in their ETC performance. In this study, we examined in detail the VO2max differences found among mitochondrial haplogroups. We recruited 81 healthy male Spanish Caucasian individuals and determined their mitochondrial haplogroup. Their VO2max was determined using incremental cycling exercise (ICE). VO2max was lower in J than in non-J haplogroup individuals (P=0.04). The H haplogroup was responsible for this difference (VO2max; J vs. H; P=0.008) and this group also had significantly higher mitochondrial oxidative damage (mtOD) than the J haplogroup (P=0.04). In agreement with these results, VO2max and mtOD were positively correlated (P=0.01). Given that ROS production is the major contributor to mtOD and consumes four times more oxygen per electron than the ETC, our results strongly suggest that ROS production is responsible for the higher VO2max found in the H variant. These findings not only contribute to a better understanding of the mechanisms underneath VO2max, but also help to explain some reported associations between mitochondrial haplogroups and mtOD with longevity, sperm motility, premature aging and susceptibility to different pathologies.