Sexual dimorphism is apparent in humans, however, to date no studies have investigated mitochondrial function focusing on intrinsic mitochondrial respiration (i.e., mitochondrial respiration for a given amount of mitochondrial protein) and mitochondrial oxygen affinity (p50_mito) in relation to biological sex in human. A skeletal muscle biopsy was donated by nine active women, and ten men matched for maximal oxygen consumption (VO_2max) and by nine endurance trained men. Intrinsic mitochondrial respiration, assessed in isolated mitochondria, was higher in women compared to men when activating complex I (CI_P) and complex I+II (CI+II_P) (p < 0.05), and was similar to trained men (CI_P, p = 0.053; CI+II_P, p = 0.066). Proton leak and p50_mito were higher in women compared to men independent of VO_2max. In conclusion, significant novel differences in mitochondrial oxidative function, intrinsic mitochondrial respiration and p50_mito exist between women and men. These findings may represent an adaptation in the oxygen cascade in women to optimize muscle oxygen uptake to compensate for a lower oxygen delivery during exercise.

Exercise has been suggested to ameliorate the detrimental effects of chemotherapy on skeletal muscle. The aim of this study was to compare the effects of different exercise regimens with usual care on skeletal muscle morphology and mitochondrial markers in patients being treated with chemotherapy for breast cancer. Specifically, we compared moderate‐intensity aerobic training combined with high‐intensity interval training (AT‐HIIT) and resistance training combined with high‐intensity interval training (RT‐HIIT) with usual care (UC). Resting skeletal muscle biopsies were obtained pre‐ and postintervention from 23 randomly selected women from the OptiTrain breast cancer trial who underwent RT‐HIIT, AT‐HIIT, or UC for 16 wk. Over the intervention, citrate synthase activity, muscle fiber cross‐sectional area, capillaries per fiber, and myosin heavy chain isoform type I were reduced in UC, whereas RT‐HIIT and AT‐HIIT were able to counteract these declines. AT‐HIIT promoted up‐regulation of the electron transport chain protein levels vs. UC. RT‐HIIT favored satellite cell count vs. UC and AT‐HIIT. There was a significant association between change in citrate synthase activity and self‐reported fatigue. AT‐HIIT and RT‐ HIIT maintained or improved markers of skeletal muscle function compared with the declines found in the UC group, indicating a sustained trainability in addition to the preservation of skeletal muscle structural and metabolic characteristics during chemotherapy. These findings highlight the importance of supervised exercise programs for patients with breast cancer during chemotherapy.—Mijwel, S., Cardinale, D. A., Norrbom, J., Chapman, M., Ivarsson, N., Wengstrom, Y., Sundberg, C. J., Rundqvist, H. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer. FASEB J. 32, 5495–5505 ((2018). www.fasebj.org

The present study investigated the effects of periodic carbohydrate (CHO) restriction on endurance performance and metabolic markers in elite endurance athletes. Twenty-six male elite endurance athletes (maximal oxygen consumption (V˙O2max), 65.0 mL O2·kg−1·min−1) completed 4 wk of regular endurance training while being matched and randomized into two groups training with (low) or without (high) CHO manipulation 3 d·wk−1. The CHO manipulation days consisted of a 1-h high-intensity bike session in the morning, recovery for 7 h while consuming isocaloric diets containing either high CHO (414 ± 2.4 g) or low CHO (79.5 ± 1.0 g), and a 2-h moderate bike session in the afternoon with or without CHO. V˙O2max, maximal fat oxidation, and power output during a 30-min time trial (TT) were determined before and after the training period. The TT was undertaken after 90 min of intermittent exercise with CHO provision before the training period and both CHO and placebo after the training period. Muscle biopsies were analyzed for glycogen, citrate synthase (CS) and β-hydroxyacyl-coenzyme A dehydrogenase (HAD) activity, carnitine palmitoyltransferase (CPT1b), and phosphorylated acetyl-CoA carboxylase (pACC). The training effects were similar in both groups for all parameters. On average, V˙O2max and power output during the 30-min TT increased by 5% ± 1% (P < 0.05) and TT performance was similar after CHO and placebo during the preload phase. Training promoted overall increases in glycogen content (18% ± 5%), CS activity (11% ± 5%), and pACC (38% ± 19%; P < 0.05) with no differences between groups. HAD activity and CPT1b protein content remained unchanged. Superimposing periodic CHO restriction to 4 wk of regular endurance training had no superior effects on performance and muscle adaptations in elite endurance athletes.

The purpose was to assess the impact of various factors on methodological errors associated with measurement of maximal oxidative phosphorylation (OXPHOS) in human skeletal muscle determined by high‐resolution respirometry in saponin‐permeabilized fibers. Biopsies were collected from 25 men to assess differences in OXPHOS between two muscle bundles and to assess the correlation between OXPHOS and the wet weight of the muscle bundle. Biopsies from left and right thighs of another five subjects were collected on two occasions to compare limbs and time‐points. A single muscle specimen was used to assess effects of the anesthetic carbocaine and the influence of technician. The difference in OXPHOS between two fiber‐bundles from the same biopsy exhibited a standard error of measurement (SEM) of 10.5 pmol · s⁻¹ · mg⁻¹ and a coefficient of variation (CV) of 15.2%. The differences between left and right thighs and between two different time‐points had SEMs of 9.4 and 15.2 pmol · s⁻¹ · mg⁻¹ and CVs of 23.9% and 33.1%, respectively. The average (±SD) values obtained by two technicians monitoring different bundles of fibers from the same biopsy were 31.3 ± 7.1 and 26.3 ± 8.1 pmol · s⁻¹ · mg⁻¹. The time that elapsed after collection of the biopsy (up to a least 5 h in preservation medium), wet weight of the bundle (from 0.5 to 4.5 mg) and presence of an anesthetic did not influence OXPHOS. The major source of variation in OXPHOS measurements is the sample preparation. The thigh involved, time‐point of collection, size of fiber bundles, and time that elapsed after biopsy had minor or no effect.

The maintenance of healthy and functional mitochondria is the result of a complex mitochondrial turnover and herein quality-control program that includes both mitochondrial biogenesis and autophagy of mitochondria. The aim of this study was to examine the effect of an intensified training load on skeletal muscle mitochondrial quality control in relation to changes in mitochondrial oxidative capacity, maximal oxygen consumption, and performance in highly trained endurance athletes. Elite endurance athletes (n = 27) performed high-intensity interval exercise followed by moderate-intensity continuous exercise 3 days per week for 4 wk in addition to their usual volume of training. Mitochondrial oxidative capacity, abundance of mitochondrial proteins, markers of autophagy, and antioxidant capacity of skeletal muscle were assessed in skeletal muscle biopsies before and after the intensified training period. The intensified training period increased several autophagy markers suggesting an increased turnover of mitochondrial and cytosolic proteins. In permeabilized muscle fibers, mitochondrial respiration was ∼20% lower after training although some markers of mitochondrial density increased by 5%–50%, indicative of a reduced mitochondrial quality by the intensified training intervention. The antioxidative proteins UCP3, ANT1, and SOD2 were increased after training, whereas we found an inactivation of aconitase. In agreement with the lower aconitase activity, the amount of mitochondrial LON protease that selectively degrades oxidized aconitase was doubled. Together, this suggests that mitochondrial respiratory function is impaired during the initial recovery from a period of intensified endurance training whereas mitochondrial quality control is slightly activated in highly trained skeletal muscle. NEW & NOTEWORTHY We show that mitochondrial respiration is temporarily impaired after a period of intensified exercise training in elite athletes. In parallel, proteins involved in the antioxidative response including SOD2, UCP3, and ANT2 were upregulated, whereas mitochondrial biogenesis was slightly activated. Despite the mitochondrial respiratory impairments, physical performance was improved a few days after the intense training period.