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.

Sarcolipin expression in human skeletal muscle: Influence of energy balance and exercise

“…The general effects of the interventions are reported with more detail in previous publications . Briefly, in the overweight walking group, the combination of caloric restriction with prolonged exercise elicited an energy deficit of 5500 kcal/day .…”

“…In contrast with rodent data, here we have demonstrated that a short training program based on repeated high‐intensity exercise reduced the SLN protein levels in vastus lateralis despite eliciting much less total energy expenditure than the 4‐day walking intervention. A principal difference between prolonged walking and repeated 30‐second all‐out sprints is the marked metabolic disturbances evoked by the sprints, which cause substantial lactic acidosis, oxidative stress, and sarcoplasmic reticulum stress . Endoplasmic reticulum stress reduces SLN expression in C2C12 cells .…”

“…To achieve these aims, we used muscle biopsies from two previous studies . The “Östersund walking study” was designed to induce a severe energy deficit of 5500 kcal/day, for 4 days, by energy restriction (3.2 kcal/kg body weight/day) and prolonged exercise (8‐hour walking).…”

“…The subjects participating in the “Östersund walking study” were overweight, allowing to test whether SLN protein expression is related to the degree of adiposity. To study the effect of high‐intensity exercise training on SLN expression in human skeletal muscle, we used biopsies obtained from volunteers of the same population that participated in a sprint training program …”

A novel mutation in nuclear prelamin a recognition factor-like causes diffuse pulmonary arteriovenous malformations

“…So far, aconitase activity is widely used as a biomarker for oxidative stress, as high-intensity exercises in humans lead to inactivation of aconitase due to ROS generation [19, 21-23]. These indicated that functional aconitase was essential in maintaining redox balance and the cellular antioxidant defense system [22]. Therefore, we inferred that deficiency of NARFL promoted production of ROS, either directly [13] or via decreased aconitase activity, resulted in iron overload [19-25].…”