Larsen 2016 FASEB J
|Larsen FJ, Schiffer TA, Ørtenblad N, Zinner C, Morales-Alamo D, Willis SJ, Calbet JA, Holmberg HC, Boushel R (2016) High-intensity sprint training inhibits mitochondrial respiration through aconitase inactivation. FASEB J 30:417-27.|
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.
• Keywords: Citrate, Exercise, Mitochondrial dysfunction, Reactive oxygen species
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Stress:Oxidative stress;RONS Organism: Human Tissue;cell: Skeletal muscle Preparation: Intact cells, Permeabilized cells, Isolated mitochondria
Coupling state: LEAK, ROUTINE, OXPHOS Pathway: N, NS HRR: Oxygraph-2k, O2k-Fluorometer