Association between mitochondrial DNA haplogroups J and K, serum branched-chain amino acids and lowered capability for endurance exercise
Kiiskilä, Jukka M.; Hassinen, Ilmo E.; Kettunen, Johannes; Kytövuori, Laura; Mikkola, Ilona; Härkönen, Pirjo; Jokelainen, Jari J.; Keinänen-Kiukaanniemi, Sirkka; Perola, Markus; Majamaa, Kari (2022-05-26)
Kiiskilä, J.M., Hassinen, I.E., Kettunen, J. et al. Association between mitochondrial DNA haplogroups J and K, serum branched-chain amino acids and lowered capability for endurance exercise. BMC Sports Sci Med Rehabil 14, 95 (2022). https://doi.org/10.1186/s13102-022-00485-3
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https://urn.fi/URN:NBN:fi-fe2022091258313
Tiivistelmä
Abstract
Background: Endurance exercise training promotes the catabolism of branched-chain amino acids (BCAAs) in skeletal muscles. We have previously shown that mitochondrial DNA (mtDNA) haplogroups J and K are markers of low responders in endurance training. In this paper, we hypothesize that BCAA catabolism is a surrogate marker of lower respiratory chain activity attributed to these haplogroups. We evaluated whether exercise-induced changes in amino acid concentrations differ between subjects harbouring mtDNA haplogroups J or K and those with non-JK haplogroups.
Methods: Finnish male conscripts (N = 633) undertook the 12-min Cooper running test at the beginning and end of their military service. The intervention during the service mainly included endurance aerobic exercise and sports-related muscle training. Concentrations of seven amino acids were analysed in the serum using a high-throughput ¹H NMR metabolomics platform. Total DNA was extracted from whole blood, and restriction fragment analysis was used to determine mtDNA haplogroups J and K.
Results: The concentrations of the seven amino acids were higher following the intervention, with the exception of phenylalanine; interestingly, the increase in the concentrations of three BCAAs was larger in subjects with haplogroup J or K than in subjects with non-JK haplogroups (p = 0.029). MtDNA haplogroups J and K share two common nonsynonymous variants. Structural analysis based on crystallographic data on bovine complexes I and III revealed that the Leu18 variant in cytochrome b encoded by m.14798T > C may interfere with ubiquinone binding at the Qi site in complex III.
Conclusions: The increase in the concentrations of serum BCAAs following exercise intervention differs between subjects harbouring mtDNA haplogroup J or K and those harbouring non-JK haplogroups. Lower response in endurance training and difference in exercise-induced increase in the concentrations of serum BCAAs suggest decreased respiratory chain activity. Haplogroups J and K share m.14798T > C in MT-CYB, which may hamper the function of complex III.
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