High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation

Filip J Larsen, Tomas A Schiffer, Niels Ørtenblad, Christoph Zinner, David Morales-Alamo, Sarah J Willis, Jose A Calbet, Hans-Christer Holmberg, Robert Boushel

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.-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.

OriginalsprogEngelsk
TidsskriftThe FASEB Journal
Vol/bind30
Udgave nummer1
Sider (fra-til)417-27
ISSN0892-6638
DOI
StatusUdgivet - jan. 2016

Fingeraftryk

Aconitate Hydratase
Respiration
Citric Acid
Exercise
Reactive Oxygen Species
Enzymes
Morale
Oxidative stress
Citric Acid Cycle
Biopsy
Mitochondrial Proteins
Quadriceps Muscle
Metabolites
Metabolism
Catalase
Homeostasis
Oxidation-Reduction
Proteins

Citer dette

Larsen, Filip J ; Schiffer, Tomas A ; Ørtenblad, Niels ; Zinner, Christoph ; Morales-Alamo, David ; Willis, Sarah J ; Calbet, Jose A ; Holmberg, Hans-Christer ; Boushel, Robert. / High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation. I: The FASEB Journal. 2016 ; Bind 30, Nr. 1. s. 417-27.
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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.-Larsen, F. J., Schiffer, T. A., {\O}rtenblad, 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.",
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Larsen, FJ, Schiffer, TA, Ørtenblad, N, Zinner, C, Morales-Alamo, D, Willis, SJ, Calbet, JA, Holmberg, H-C & Boushel, R 2016, 'High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation', The FASEB Journal, bind 30, nr. 1, s. 417-27. https://doi.org/10.1096/fj.15-276857

High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation. / Larsen, Filip J; Schiffer, Tomas A; Ørtenblad, Niels; Zinner, Christoph; Morales-Alamo, David; Willis, Sarah J; Calbet, Jose A; Holmberg, Hans-Christer; Boushel, Robert.

I: The FASEB Journal, Bind 30, Nr. 1, 01.2016, s. 417-27.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation

AU - Larsen, Filip J

AU - Schiffer, Tomas A

AU - Ørtenblad, Niels

AU - Zinner, Christoph

AU - Morales-Alamo, David

AU - Willis, Sarah J

AU - Calbet, Jose A

AU - Holmberg, Hans-Christer

AU - Boushel, Robert

N1 - © FASEB.

PY - 2016/1

Y1 - 2016/1

N2 - 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.-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.

AB - 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.-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.

U2 - 10.1096/fj.15-276857

DO - 10.1096/fj.15-276857

M3 - Journal article

C2 - 26452378

VL - 30

SP - 417

EP - 427

JO - F A S E B Journal

JF - F A S E B Journal

SN - 0892-6638

IS - 1

ER -