title: High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation.
abstract: 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 H2O2 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 H2O2 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.
authors.affiliation: *Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; Swedish School of Sport and Health Sciences, Stockholm, Sweden; Institute of Sports Science and Clinical Biomechanics, Muscle Research Cluster, University of Southern Denmark, Odense, Denmark; Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden; Department of Sport Science, Julius Maximilians University, Würzburg, Germany; Research Institute of Biomedical and Health Sciences (IUIBS), Las Palmas de Gran Canaria, Canary Islands, Spain; and School of Kinesiology, University of British Columbia, Vancouver, British Columbia, Canada filip.larsen@ki.se filip.larsen@gih.se.
authors.forename: Filip J
authors.initials: FJ
authors.lastname: Larsen
authors.affiliation: *Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; Swedish School of Sport and Health Sciences, Stockholm, Sweden; Institute of Sports Science and Clinical Biomechanics, Muscle Research Cluster, University of Southern Denmark, Odense, Denmark; Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden; Department of Sport Science, Julius Maximilians University, Würzburg, Germany; Research Institute of Biomedical and Health Sciences (IUIBS), Las Palmas de Gran Canaria, Canary Islands, Spain; and School of Kinesiology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Tomas A
authors.initials: TA
authors.lastname: Schiffer
authors.affiliation: *Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; Swedish School of Sport and Health Sciences, Stockholm, Sweden; Institute of Sports Science and Clinical Biomechanics, Muscle Research Cluster, University of Southern Denmark, Odense, Denmark; Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden; Department of Sport Science, Julius Maximilians University, Würzburg, Germany; Research Institute of Biomedical and Health Sciences (IUIBS), Las Palmas de Gran Canaria, Canary Islands, Spain; and School of Kinesiology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Niels
authors.initials: N
authors.lastname: Ørtenblad
authors.affiliation: *Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; Swedish School of Sport and Health Sciences, Stockholm, Sweden; Institute of Sports Science and Clinical Biomechanics, Muscle Research Cluster, University of Southern Denmark, Odense, Denmark; Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden; Department of Sport Science, Julius Maximilians University, Würzburg, Germany; Research Institute of Biomedical and Health Sciences (IUIBS), Las Palmas de Gran Canaria, Canary Islands, Spain; and School of Kinesiology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Christoph
authors.initials: C
authors.lastname: Zinner
authors.affiliation: *Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; Swedish School of Sport and Health Sciences, Stockholm, Sweden; Institute of Sports Science and Clinical Biomechanics, Muscle Research Cluster, University of Southern Denmark, Odense, Denmark; Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden; Department of Sport Science, Julius Maximilians University, Würzburg, Germany; Research Institute of Biomedical and Health Sciences (IUIBS), Las Palmas de Gran Canaria, Canary Islands, Spain; and School of Kinesiology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Morales-Alamo
authors.affiliation: *Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; Swedish School of Sport and Health Sciences, Stockholm, Sweden; Institute of Sports Science and Clinical Biomechanics, Muscle Research Cluster, University of Southern Denmark, Odense, Denmark; Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden; Department of Sport Science, Julius Maximilians University, Würzburg, Germany; Research Institute of Biomedical and Health Sciences (IUIBS), Las Palmas de Gran Canaria, Canary Islands, Spain; and School of Kinesiology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Willis
authors.affiliation: *Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; Swedish School of Sport and Health Sciences, Stockholm, Sweden; Institute of Sports Science and Clinical Biomechanics, Muscle Research Cluster, University of Southern Denmark, Odense, Denmark; Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden; Department of Sport Science, Julius Maximilians University, Würzburg, Germany; Research Institute of Biomedical and Health Sciences (IUIBS), Las Palmas de Gran Canaria, Canary Islands, Spain; and School of Kinesiology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Calbet
authors.affiliation: *Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; Swedish School of Sport and Health Sciences, Stockholm, Sweden; Institute of Sports Science and Clinical Biomechanics, Muscle Research Cluster, University of Southern Denmark, Odense, Denmark; Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden; Department of Sport Science, Julius Maximilians University, Würzburg, Germany; Research Institute of Biomedical and Health Sciences (IUIBS), Las Palmas de Gran Canaria, Canary Islands, Spain; and School of Kinesiology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Hans-Christer
authors.initials: HC
authors.lastname: Holmberg
authors.affiliation: *Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden; Swedish School of Sport and Health Sciences, Stockholm, Sweden; Institute of Sports Science and Clinical Biomechanics, Muscle Research Cluster, University of Southern Denmark, Odense, Denmark; Swedish Winter Sports Research Centre, Department of Health Sciences, Mid Sweden University, Östersund, Sweden; Department of Sport Science, Julius Maximilians University, Würzburg, Germany; Research Institute of Biomedical and Health Sciences (IUIBS), Las Palmas de Gran Canaria, Canary Islands, Spain; and School of Kinesiology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Boushel
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism*; D000328:Adult; D019069:Cell Respiration; D002478:Cells, Cultured; D019343:Citric Acid / Q000378:metabolism; D015444:Exercise; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress; D005082:Physical Exertion
chemical_list: D019343:Citric Acid; D006861:Hydrogen Peroxide; D000154:Aconitate Hydratase
keywords: citrate; exercise; mitochondrial dysfunction; reactive oxygen species