Bioenergetic adaptations in Cpt2Sk−/−oxidative muscles result in a glycolytic metabolic phenotype. (A) Maximum rates of substrate-supported oxygen consumption (JO2) in isolated mitochondria from control glycolytic and oxidative muscles under low energy demands; PC = palmitoylcarnitine, OCT = octanoylcarnitine, PYR = pyruvate, S = succinate, M = malate, and ROT = rotenone. (B) Same as A but under high energy demands. (C) Oxygen consumption fold-change from low to high energy demands in control glycolytic and oxidative muscle mitochondria. (D) Same as A for mitochondria isolated from Cpt2Sk−/− glycolytic and oxidative muscles. (E) Same as D under high energy demands. (F) Same as C for Cpt2Sk−/− mitochondria. (G) Comparison of mitochondrial oxygen consumption rates at low energy demands between genotypes for glycolytic and oxidative muscles presented as Cpt2Sk−/− percentage change from control. (H) Same as G under high energy demands. (I) Max speed reached during a high-intensity treadmill-based exercise test. All data are presented as Mean ± SEM. For (A) to (F), n = 3–6 and ∗P ≤ 0.05 by T-test between glycolytic and oxidative muscle mitochondria for each substrate within the same genotype. For (G) and (H), n = 3–6 and ∗P ≤ 0.05 by T-test between control and Cpt2Sk−/− muscle mitochondria for each substrate within the same energy demand. For (I) n = 5 and ∗P ≤ 0.05 by T-test between genotypes.