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High‐intensity sprint training inhibits mitochondrial respiration through aconitase inactivation
Author(s) -
Larsen Filip J.,
Schiffer Tomas A.,
Ørtenblad Niels,
Zinner Christoph,
MoralesAlamo David,
Willis Sarah J.,
Calbet Jose A.,
Holmberg HansChrister,
Boushel Robert
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.15-276857
Subject(s) - aconitase , oxidative stress , citrate synthase , mitochondrion , sod2 , reactive oxygen species , mitochondrial ros , oxidative phosphorylation , mitochondrial biogenesis , chemistry , catalase , biochemistry , biology , microbiology and biotechnology , enzyme , superoxide dismutase
Intense exercise training is a powerful stimulus that activates mitochondrial biogenesis pathways and thus increases mitochondrial density and oxidative capacity. Moderate levels of reactive oxygen species (ROS) during exercise are considered vital in the adaptive response, but high ROS production is a serious threat to cellular homeostasis. Although biochemical markers of the transition from adaptive to maladaptive ROS stress are lacking, it is likely mediated by redox sensitive enzymes involved in oxidative metabolism. One potential enzyme mediating such redox sensitivity is the citric acid cycle enzyme aconitase. In this study, we examined biopsy specimens of vastus lateralis and triceps brachii in healthy volunteers, together with primary human myotubes. An intense exercise regimen inactivated aconitase by 55‐72%, resulting in inhibition of mitochondrial respiration by 50‐65%. In the vastus, the mitochondrial dysfunction was compensated for by a 15‐72% increase in mitochondrial proteins, whereas H 2 O 2 emission was unchanged. In parallel with the inactivation of aconitase, the intermediary metabolite citrate accumulated and played an integral part in cellular protection against oxidative stress. In contrast, the triceps failed to increase mitochondrial density, and citrate did not accumulate. Instead, mitochondrial H 2 O 2 emission was decreased to 40% of the pretraining levels, together with a 6‐fold increase in protein abundance of catalase. In this study, a novel mitochondrial stress response was highlighted where accumulation of citrate acted to preserve the redox status of the cell during periods of intense exercise.—Larsen, F. J., Schiffer, T. A., Ørtenblad, N., Zinner, C., Morales‐Alamo, D., Willis, S. J., Calbet, J. A., Holmberg, H.‐C., Boushel, R. High‐intensity sprint training inhibits mitochondrial respiration through aconitase inactivation. FASEB J. 30, 417‐427 (2016). www.fasebj.org