Training at high exercise intensity promotes qualitative adaptations of mitochondrial function in human skeletal muscle

Frédéric N. Daussin, Joffrey Zoll, Elodie Ponsot, Stéphane P. Dufour, Stéphane Doutreleau, Evelyne Lonsdorfer, Renée Ventura-Clapier, Bertrand Mettauer, François Piquard, Bernard Geny, Ruddy Richard


This study explored mitochondrial capacities to oxidize carbohydrate and fatty acids and functional optimization of mitochondrial respiratory chain complexes in athletes who regularly train at high exercise intensity (ATH, n = 7) compared with sedentary (SED, n = 7). Peak O2 uptake (V̇o2max) was measured, and muscle biopsies of vastus lateralis were collected. Maximal O2 uptake of saponin-skinned myofibers was evaluated with several metabolic substrates [glutamate-malate (V̇GM), pyruvate (V̇Pyr), palmitoyl carnitine (V̇PC)], and the activity of the mitochondrial respiratory complexes II and IV were assessed using succinate (V̇s) and N,N,N′,N′-tetramethyl-p-phenylenediamine dihydrochloride (V̇TMPD), respectively. V̇o2max was higher in ATH than in SED (57.8 ± 2.2 vs. 31.4 ± 1.3 ml·min−1·kg−1, P < 0.001). V̇GM was higher in ATH than in SED (8.6 ± 0.5 vs. 3.3 ± 0.3 μmol O2·min−1·g dry wt−1, P < 0.001). V̇Pyr was higher in ATH than in SED (8.7 ± 1.0 vs. 5.5 ± 0.2 μmol O2·min−1·g dry wt−1, P < 0.05), whereas V̇PC was not significantly different (5.3 ± 0.9 vs. 4.4 ± 0.5 μmol O2·min−1·g dry wt−1). V̇S was higher in ATH than in SED (11.0 ± 0.6 vs. 6.0 ± 0.3 μmol O2·min−1·g dry wt−1, P < 0.001), as well as V̇TMPD (20.1 ± 1.0 vs. 16.2 ± 3.4 μmol O2·min−1·g dry wt−1, P < 0.05). The ratios V̇S/V̇GM (1.3 ± 0.1 vs. 2.0 ± 0.1, P < 0.001) and V̇TMPD/V̇GM (2.4 ± 1.0 vs. 5.2 ± 1.8, P < 0.01) were lower in ATH than in SED. In conclusion, comparison of ATH vs. SED subjects suggests that regular endurance training at high intensity promotes the enhancement of maximal mitochondrial capacities to oxidize carbohydrate rather than fatty acid and induce specific adaptations of the mitochondrial respiratory chain at the level of complex I.

  • metabolism
  • exercise training

skeletal muscle is a highly malleable tissue, capable of pronounced metabolic and morphological adaptations in response to contractile activity (i.e., exercise) (17). Endurance training induces marked metabolic and structural adaptations in skeletal muscle, with an increase in mitochondrial mass and capillary density (19). In parallel with these quantitative improvements, some mitochondrial qualitative changes seem to participate in the mitochondrial adaptations, allowing increased exercise performance (40, 45). Our laboratory previously demonstrated that, in addition to increased muscle oxidative capacities, the highest fitness levels are accompanied by a tighter control of respiration by phosphate acceptors and by an increased role of the creatine kinase system, providing a more efficient servo-control of energy production to energy expenditure (43, 45).

Mitochondrial adaptations to endurance training lead to a greater absolute capacity to oxidize all fuel substrates, including carbohydrates (CHO) and fatty acids (FA). The relative contribution of each fuel varies with exercise intensity (4, 8, 30) and training status (5, 9, 20, 21), and CHO are known to be primarily used during high-intensity exercise, independent of fitness level (6, 24, 30). Nevertheless, it has been shown that trained subjects rely less on CHO for fuel than do untrained subjects, even during exercise performed at similar relative high intensity (10, 39). In regard to training adaptations, it is well known that short-term endurance training induces an improvement in the capacity to oxidize lipids during moderate exercise intensity (9, 10, 36). Although endurance training at mixed exercise intensity has been documented to improve mitochondrial function (40), no studies directly compared the relative contribution of each fuel in the mitochondrial function of athletes who trained regularly at a velocity associated with the second ventilatory threshold with sedentary subjects.

Our laboratory recently demonstrated on a murine model the existence of a mitochondrial tissue specificity of substrate oxidation as a function of muscle fiber type (28). Therefore, exploration of the intrinsic mitochondrial capacities to oxidize CHO and lipid may represent a means to visualize the muscular adaptations of metabolic pathways as a function of the training status and training intensity.

Mitochondria oxidize pyruvate and FA into NADH and/or FADH2. These reduced equivalents are oxidized further by the mitochondrial respiratory chain to establish an electrochemical gradient of protons, which is finally used by the ATP synthase to rephosphorylate ADP into ATP. It has been suggested that the increase of some respiratory complex activities could allow the optimization of enzyme ratios along the different mitochondrial respiratory chain complexes (13), which could ameliorate the cellular homeostasis during exercise. However, to date, no study explored the possible adaptations of mitochondrial respiratory chain complexes in human skeletal muscle when muscular activity is highly increased chronically. We hypothesized that, concomitantly with a higher capacity to oxidize CHO, there could be some specific adaptations in the activities of the respiratory complexes in athletes who regularly train at high intensities.

Therefore, this study explored qualitative adaptations at two crucial steps of the mitochondrial machinery in skeletal muscle of athletes (ATH) who trained at high intensity vs. sedentary (SED) human subjects throughout a cross-sectional study. 1) We explored the intrinsic functional capacities of mitochondria to oxidize FA and CHO to determine the long-term adaptations of potentialities for fuel preferences. 2) We investigated the specific adaptations at the level of the mitochondrial respiratory chain complexes.



Seven SED individuals and seven ATH, all men, participated in the study (Table 1). All subjects were informed about the potential risks associated with the experiment before giving their written consent to participate. ATH were engaged in a regular training schedule comprising five training session per week for more than 2 yr, including two weekly training session performed at high intensity. Their respective individual training schedule remained unaltered during the 3 wk preceding the experimental period. The investigation was approved by the Consultant Committee on Human Protection from Biomedical Research of Strasbourg, in accordance with the French Law and with the Declaration of Helsinki. It is important to note that the results are obtained with men, and they cannot be generalized to women.

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Table 1.

Group characteristics

Study Design

Incremental exercise tests.

Each subject performed an incremental exercise test (IET) to exhaustion to determine the peak power output, peak oxygen uptake (V̇o2max), and ventilatory thresholds. IET were performed in an upright position on an electronically braked cycle ergometer (Medifit 1000S, Belgium). Pedaling frequency was 60–70 revolutions/min and was maintained constant during the test. We used the Hansen equations (15) to determine the maximal theoretical power for SED and ATH subjects and designed the power increments to be individually adjusted so that exhaustion always occur within 12–15 min. The first ventilatory threshold [i.e., lactate threshold (LT)] was determined graphically (2), from a regression analysis of the slope of the carbon dioxide elimination (V̇co2) vs. oxygen consumption (V̇o2) plot. Heart rate and V̇o2 were monitored continuously during the test. Blood lactate was collected immediately at exhaustion and in recovery (1st, 3rd, and 5th min).

Ventilatory parameters.

During the tests, V̇o2 was measured on a breath-by-breath basis using an open-circuit metabolic cart with rapid O2 and CO2 analyses (breath-by-breath metabolic measurement, Sensor Medics, MSE, Yorba Linda, CA). V̇o2max was defined as the highest 30-s average V̇o2 value.

Evaluation of ATH training sessions.

The average training schedule of ATH is given in Table 2 for the 3 wk preceding the study. All ATH were asked to report their individual training schedule into detailed training logs, including duration, distance, and intensity of each training sessions, providing both quantitative and qualitative characterization of the overall training load. Duration and intensity of the training sessions were assessed based on the running velocity spread out in four intensity zones: low exercise intensity < LT < moderate exercise intensity < respiration compensatory point < heavy exercise intensity < V̇o2max < severe exercise intensity.

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Table 2.

Training load characteristics of trained subjects

Metabolic parameters.

During IET tests, 2-ml blood samples were collected into iced tubes for immediate determination of blood LA concentration (Chiron-Diagnostics Serie 800, Bayer, Puteau, France).

Skeletal muscle biopsy.

Vastus lateralis muscle was obtained by the percutaneous Bergström technique after local anesthesia, as previously described (25). Biopsy was taken 48 h after IET, and subjects were asked to refrain from strenuous exercise during this period. The muscle tissue retrieved was rinsed in ice-cold saline and was used for in situ respiration studies.

In situ study of mitochondrial respiration.

The mitochondrial respiration was studied in situ in saponin-skinned fibers. Briefly, fibers were separated under a binocular microscope in solution S at 4°C (see below) and permeabilized in solution S with 50 μg/ml of saponin for 30 min. After being placed 10 min in solution R (see below) to wash out adenine nucleotides and creatine phosphate, skinned separated fibers were transferred in a 3-ml water-jacketed oxygraphic cell (Strathkelvin Instruments, Glasgow, UK) equipped with a Clark electrode, as previously described (21). Solutions R and S contained the following: 2.77 mM CaK2EGTA, 7.23 mM K2EGTA (100 nM free Ca2+), 6.56 mM MgCl2 (1 mM free Mg2+), 20 mM taurine, 0.5 mM DTT, 50 mM potassium-methane sulfonate (160 mM ionic strength), and 20 mM imidazole (pH 7.1). Solution S also contained 5.7 mM Na2ATP, 15 mM creatine-phosphate, while solution R contained 5 mM glutamate, 2 mM malate, 3 mM phosphate, and 2 mg/ml FA free bovine serum. After the experiments, fibers were harvested and dried, and respiration rates were expressed as micromoles of O2 per minute per gram dry weight. Solution R was similar to solution R without substrates and was used to determined maximal V̇o2 rate for the substrates.

Measurement of the maximal muscular oxidative capacities.

The ADP-stimulated respiration above basal V̇o2 (V̇0) was measured by addition of 2 mM of ADP. After the determination of the V̇0, the maximal fiber respiration rates (V̇max) were measured at 22°C under continuous stirring in the presence of saturating amount of ADP (2 mM) as phosphate acceptor and glutamate-malate as mitochondrial substrates (V̇GM). The acceptor control ratio was V̇GM/V̇0 and represents the degree of coupling between oxidation and phosphorylation.

Measurements of the substrate oxidative capacities.

In separates samples, additions of glycerol-3-phosphate (1.2 mM), pyruvate (1 mM), or palmitoyl-carnitine (135 μM) were done in solution R in the presence of 2 mM ADP, and maximal V̇o2 rate for these substrates was determined (V̇G3P, V̇Pyr, and V̇PC, respectively). Malate (2 mM) was added with pyruvate and palmitoyl-carnitine to initiate the Krebs cycle.

Measurement of the respiratory chain complexes.

When V̇GM was recorded, electron flow goes through complexes I, III, and IV. Then 4 min after this V̇GM measurement, the complex I was blocked with amytal (2 mM), and then complex II was stimulated with succinate (25 mM). In these conditions, mitochondrial respiration was evaluated by complexes II, III, and IV (V̇S). After that, N,N,N′,N′-tetramethyl-p-phenylenediamine dihydrochloride (TMPD, 0.5 mM) and ascorbate (0.5 mM) were added as an artificial electron donor to cytochrome-c. In these conditions, cytochrome-c oxidase (complex IV) was studied as an isolated step of respiratory chain (V̇TMPD). The ratios V̇S/V̇GM and V̇TMPD/V̇GM allow exploration of complexes I, II, and IV in ATH vs. SED men.


Data are presented as means ± SE. Statistical analyses were performed using Sigma Stat for Windows (version 3.0, SPSS, Chicago, IL). After testing for data distribution normality and variance homogeneity, we used analysis of covariance to adjust group differences for baseline covariates (weight and age). The significance level was set at P < 0.05.


Subject Characteristics

Subjects' characteristics are given in Table 1. As calculated by Hansen's formulas, the predicted V̇o2max was not significantly different between SED and ATH. But by design, the V̇o2max was 89 ± 4% of the predicted V̇o2max, as calculated by Hansen's formula in SED, and 155 ± 4% of predicted V̇o2max in ATH (significantly different from SED, P < 0.001) (41). It is important to notice that, even if ATH trained 79% of total training time at low and moderate intensities, they trained 21% of total training time at very high and severe intensities (Table 2).

Exercise Tests

Table 3 reports the parameters of aerobic performance capacity, as measured during the incremental symptom-limited exercise test. At LT, the V̇o2 expressed in relative values was significantly higher in ATH than in SED (P < 0.001). At peak exercise, V̇o2max was much greater in ATH than in SED, according to the fitness differences, but the respiratory exchange ratio remained similar and >1.1, and LA was >8 mmol/l for both groups, suggesting that all of the subjects reached exhaustion during their IET. As expected, the peak LA was higher in ATH (P < 0.05).

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Table 3.

Gas exchanges during the incremental exercise test

Mitochondrial Substrate Utilization

To compare skeletal muscle oxidative capacities of SED and ATH subjects, we measured the maximal respiratory rates of in situ mitochondria in vastus lateralis samples to determine V̇max with different substrates, as well as the functional activities of the respiratory chain complexes. These parameters allow an exhaustive characterization of muscle maximal oxidative capacities with a given substrate, reflecting both mitochondrial density, as well as the functional properties of skeletal muscle mitochondria.

max with the different mitochondrial substrates are presented in Fig. 1. V̇G3P was low compared with V̇pyr and V̇PC and not significantly different among groups. V̇GM was dramatically higher (+156%) in ATH than in SED subjects (8.6 ± 0.5 vs. 3.3 ± 0.3 μmol O2·min−1·g dry wt−1, P < 0.001). On the other hand, V̇PC was not significantly different between ATH and SED (5.3 ± 0.9 vs. 4.4 ± 0.5 μmol O2·min−1·g dry wt−1, P = 0.37). V̇Pyr was also significantly higher (+58%) in ATH than in SED subjects (8.7 ± 1.0 vs. 5.5 ± 0.2 μmol O2·min−1·g dry wt−1, P < 0.05). When comparing the different substrate pathways, V̇Pyr was significantly higher than V̇PC in ATH (+64%, P < 0.05), which was not the case for SED.

Fig. 1.

Maximal mitochondrial respiration (V̇max) of saponin-skinned fibers of skeletal muscle of sedentary subjects (SED; open bars) and athletes (ATH; solid bars) obtained with 4 different substrates: V̇G3P, V̇PC, V̇GM, and V̇Pyr. The substrates used were as follows: G3P, glycerol-3-phosphate; PC, palmitoyl carnitine; M, malate; G, glutamate; Pyr, pyruvate. Values are means ± SE. Significantly different from SED: *P < 0.05; ***P < 0.001. §Significantly different from PC+M: P < 0.05.

We measured maximal activity of the different complexes of the mitochondrial regulatory chain (Fig. 2). With succinate as electron donor for complex II, V̇S was significantly higher in ATH (+84%) than in SED subjects (11.0 ± 0.6 vs. 6.0 ± 0.3 μmol O2·min−1·g dry wt−1, P < 0.001). Complex IV (TMPD-ascorbate as electron donor) respiratory rates were significantly higher in ATH (+24%) than in SED (20.1 ± 1.0 vs. 16.2 ± 3.4 μmol O2·min−1·g dry wt−1, P < 0.05). The ratios V̇S/V̇GM and V̇TMPD/V̇GM showed the specific adaptations of the mitochondrial complexes I, II, and IV in skeletal muscle of both groups. V̇S/V̇GM (1.3 ± 0.1 vs. 2.0 ± 0.1, P < 0.001), as well as V̇TMPD/V̇GM (2.4 ± 1.0 vs. 5.2 ± 1.8, P < 0.01) were significantly lower in ATH than in SED, suggesting that the excess of complexes II and IV activities compared with complex I activity was proportionally lower in ATH than in SED.

Fig. 2.

A: evaluation of mitochondrial respiratory chain complexes of saponin-skinned fibers of skeletal muscle of SED (open bars) and ATH (solid bars) with succinate (V̇S; complexes II, III, and IV), glutamate-malate (V̇GM; complexes I, III, and IV), and N,N,N′,N′-tetramethyl-p-phenylenediamine dihydrochloride-ascorbate (V̇TMPD; complex IV). B: ratios V̇S/V̇GM and V̇TMPD/V̇GM show the relative adaptation of complexes I, II, and IV in athletes. Results are expressed as means ± SE. Significantly different from SED: *P < 0.05; **P < 0.01, ***P < 0.001.

Figure 3 shows the acceptor control ratio (V̇max/V̇0). This parameter was significantly higher in ATH than in SED (5.4 ± 0.5 vs. 3.1 ± 0.5, P < 0.01). These results are in accordance with a previous study (45) and suggest an improvement in the coupling between the electron transport chain and the phosphorylation.

Fig. 3.

Coupling between mitochondrial oxidation and phosphorylation [acceptor control ratio (ACR), V̇GM/V̇0] in saponin-skinned fibers of skeletal muscle of SED (open bar) and ATH (solid bar). V̇0, basal mitochondrial respiration. Results are expressed as means ± SE. **Significantly different from SED: P < 0.01.


The objective of this study was to compare the mitochondrial function at crucial steps of the mitochondrial machinery between endurance ATH who trained at high exercise intensity and SED subjects. The main results of this study show that the intrinsic mitochondrial capacity to oxidize CHO (i.e., V̇Pyr) is higher in ATH than in SED subjects, whereas the mitochondrial capacity to oxidize lipids (i.e., V̇PC) is not significantly different in both groups. These results support the notion that, besides a quantitative increase in the oxidative capacities, mitochondria also develop adaptations allowing for a specific increase in the mitochondrial capacity to oxidize CHO rather than lipids in ATH who regularly trained at high intensity. Moreover, ATH exhibited lower ratios of complex II and IV to complex I compared with SED subjects, suggesting an optimization of the complex I of the respiratory chain, which could be implicated in the better mitochondrial function observed in ATH.

Regular endurance training induces numerous physiological adaptations, ultimately improving exercise capacity. Previous studies observed alterations in mitochondrial function with endurance training (27, 33, 36, 37, 44, 45). One of the most characteristic adaptations to training is a change in skeletal muscle substrate metabolism (16). Training-induced shift in substrate utilization is classically attributed to the improved muscular oxidative capacities that result from an increase in mitochondrial density (16). However, other factors must also contribute to the training response, as shown in studies in which metabolism (14) or performance was altered (11, 42), despite no change in muscle oxidative capacities. There is a long-standing notion that endurance training causes a shift from predominantly CHO oxidation toward fat oxidation (16). Accordingly, Cogan et al. (9, 10) found that the rate of utilization of plasma glucose is lower in trained than in untrained subjects during moderate- to high-intensity exercise for a given absolute load, and also when the exercise is performed at the same relative (and, therefore, a higher absolute) intensity. For instance, cyclists and triathletes who trained at least 4 times/wk for 2 h or more and had a training history of at least 5 yr show a higher rate of fat oxidation and an increased relative contribution of fat compared with untrained subjects for an exercise at the same relative intensity (60% of V̇o2max) (21). Conversely, O'Brien et al. (26) demonstrate that, during marathon running at 73.3 or 64.5% of V̇o2max, CHO is the primary fuel used. In the same way, Brooks and Mercier (6) have hypothesized that there is a “crossover” effect, such that, during acute exercise at high intensity, the rate of glucose utilization is greater in trained than in untrained subjects, and the rate of glucose uptake increases exponentially with increasing exercise intensity.

In this study, we measured maximal mitochondrial respiration using different substrates, which allow the characterization of mitochondrial fuel preferences for aerobic energy production. Interestingly, we found that mitochondrial intrinsic capacities to oxidize pyruvate (i.e., CHO pathway) are significantly higher than the capacity to oxidize palmitoyl carnitine (i.e., lipid pathway) in ATH who regularly trained at high exercise intensity. These results are in accordance with a recent study of Sahlin et al. (33), which observed that both trained and untrained subject present higher capacity to oxidize pyruvate than palmitoyl carnitine. Moreover, the capacity to use palmitoyl carnitine was not different between ATH and SED. This suggests that mitochondria of ATH exhibited a higher capacity to oxidize CHO than lipid, which was not the case in SED. Indeed, in ATH, maximal mitochondrial respiration with palmitoyl carnitine represents only 60% of the maximal oxidative capacities established with pyruvate and glutamate-malate as substrates. These results substantiate the crossover concept, suggesting that the increased use of CHO during heavy exercise training leads to intrinsic muscular mitochondrial adaptations, promoting the utilization of substrates from the CHO pathways. In fact, high- and very-high-intensity training (20 and 1% of their training duration, respectively) may presumably induce specific metabolic adaptations, different from the adaptations following moderate exercise training. In the same way, the maximal capacity of muscle to transport and phosphorylate glucose during exercise is higher in the trained state, and regular training increases muscle glucose transporter number and hexokinase activity and reduces the intramuscular glucose-6-phosphate concentration during exercise (12). Accordingly, Kjaer et al. (22) reported that the rate of glucose appearance in blood was higher in endurance athletes than in untrained men during exercise at 60–110% of V̇o2max. We found that the functional capacity of mitochondria to oxidize FA was not different between SED and ATH. These results are in line with a molecular study showing similar amounts of mRNAs coding for enzymes involved in the β-oxidation of long-chain FA in tibialis anterior muscle of trained and untrained subjects (34). It is also in accordance with the fact that our ATH, in their competitions, perform at intensities that elicit >80% of V̇o2max, which require mainly CHO oxidation as energy source (6, 38). Thus long-term training at high intensities seems to influence the athlete skeletal muscle profile toward increased mitochondrial capacities to oxidize CHO but not lipids.

It is well known that ATH subjects had a significantly higher myosin heavy chain I percentage and a significantly lower myosin heavy chain IIx percentage than SED subjects (45), and it has been shown that slow-twitch fibers (vs. fast-twitch fibers) have higher activities of enzymes involved in FA oxidation (1). Then we could hypothesize that contractile phenotype could also influence the adaptations of muscular oxidative capacities in our ATH. In case of low-intensity training, substrate oxidation seems to be influenced by fiber-type composition, but not by training status (33). Because our ATH who trained at high intensity increased the capacity to oxidize CHO but not FA, we can suggest that training at high intensity, in contrast to low intensity, promotes muscular CHO oxidation.

Our result could appear in contradiction with the generally well-accepted concept that endurance exercise training leads to a shift of skeletal muscle mitochondria toward an increased use of lipids as a substrate source (for review, see Ref. 18). However, we agree that endurance-trained subjects could use more lipids, both at the same absolute and at the same relative exercise intensity (39), and that higher ADP sensitivity with palmitoyl carnitine than that with pyruvate may influence fuel utilization at low rate of respiration in favor of lipid oxidation (33). Our study provides complementary results, suggesting that mitochondrial adaptations are in favor of higher CHO oxidation capacities in the specific case where subjects regularly train at high intensities. Moreover, further investigations in athletes training at different intensities are needed to explore the role of training intensity in the determination of muscle mitochondrial metabolic profile.

Next to the enhanced capacity to oxidize CHO (i.e., pyruvate), we postulated that high-intensity training could induce some alterations at the level of the mitochondrial respiratory chain complexes to increase the control of mitochondrial respiration (32). The calculation of the ratio of mitochondrial complex activities shows the relative contribution of mitochondrial complexes I, II, and IV in skeletal muscle of both groups. The complex II-to-I ratio, as well as complex IV-to-I ratio were significantly lower in ATH than in SED, suggesting an increase complex I activity compared with complex II and IV in ATH subjects. Because complex I is one of the main limiting steps for the mitochondrial metabolic fluxes in skeletal muscle (32), its augmentation could reflect an improvement in the control coefficient of the respiratory chain (31), allowing amelioration in the rate of NADH oxidation, to support higher CHO oxidation rates. All together, we can postulate that these specific mitochondrial adaptations participate in the increased exercise performance during ATH competition.

Limitations of the Study

Because ATH carried out both moderate and high exercise intensities, we cannot completely rule out that moderate exercise sessions did not participate in the qualitative mitochondrial muscular adaptations. Nevertheless, because of the fact that it has been shown that moderate exercise training preferentially increases fat oxidation capacity (3, 7, 9, 23, 35), together with the fact that muscle glycogen oxidation increased in relation to exercise intensity (30), we can postulate that the muscular adaptations favoring CHO metabolism observed in our ATH were predominantly induced by the high-intensity training sessions. This work is a cross-sectional study rather than a longitudinal study, and thus we cannot definitively state that the high-intensity part of the training program was responsible for the observed alterations. Indeed, there may be a difference in baseline mitochondrial function (before high-intensity training) that would not be captured by this study and could participate in the difference in the mitochondrial function between SED and ATH. Then a longitudinal study exploring the mitochondrial adaptations following high-intensity training needs to be carried out to completely rule out this possibility.


This cross-sectional study suggests that, in addition to higher skeletal muscle oxidative capacities, important qualitative adaptations take place at the level of substrate utilization. In the particular situation where subjects regularly train at high exercise intensity, there seems to be some mitochondrial adaptations favoring the CHO pathway over the lipid pathway for the highest energetic fluxes, and improving the control of mitochondrial metabolic fluxes through improvement of mitochondrial complex I activity compared with complex II and IV.


This research was supported by the Clinical Research Department of Strasbourg's civil hospital and financed by the French Ministry for Heath and Solidarity with a Regional Hospital Protocol of Clinical Research (2002), and by the International Olympic Committee.


  • * F. N. Daussin and J. Zoll contributed equally to this work.

  • The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


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