Lack of myostatin alters intermyofibrillar mitochondria activity, unbalances redox status, and impairs tolerance to chronic repetitive contractions in muscle.
Loss of myostatin (mstn) function leads to a decrease in mitochondrial content, a reduced expression of cytochrome c oxidase, and a lower citrate synthase activity in skeletal muscle. These data suggest functional or ultrastructural mitochondrial abnormalities that can impact on muscle endurance characteristics in such phenotype. To address this issue, we investigated subsarcolemmal and intermyofibrillar (IMF) mitochondrial activities, skeletal muscle redox homeostasis, and muscle fiber endurance quality in mstn-deficient mice [mstn knockout (KO)]. We report that lack of mstn induced a decrease in the coupling of IMF mitochondria respiration, with significantly higher basal oxygen consumption. No lysis of mitochondrial cristae or excessive swelling were observed in mstn KO mice compared with wild-type (WT) mice. Concerning redox status, mstn KO gastrocnemius exhibited a significant decrease in lipid peroxidation levels (-56%; P < 0.01 vs. WT) together with a significant upregulation of the antioxidant glutathione system. In contrast, superoxide dismutase and catalase activities were altered in mstn KO, gastrocnemius and soleus with a reduction of up to 80% compared with WT animals. The force production observed after contractile endurance test was significantly lower in extensor digitorum longus and soleus muscles of mstn KO mice compared with the controls (17 ± 3 and 36 ± 5% vs. 28 ± 4 and 56 ± 5%, respectively, P < 0.05). Together, these findings indicate that, besides an increased skeletal muscle mass, genetic mstn inhibition has differential effects on redox homeostasis and mitochondrial function that would have functional consequences on muscle response to endurance exercise.
Institut National de la Recherche Agronomique, Dynamique Musculaire et Métabolisme, Montpellier, France.
Claire
C
Ploquin
Béatrice
B
Chabi
Gilles
G
Fouret
Barbara
B
Vernus
Christine
C
Feillet-Coudray
Charles
C
Coudray
Anne
A
Bonnieu
Christelle
C
Ramonatxo
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002950:Citrate (si)-Synthase / Q000378:metabolism; D017079:Exercise Tolerance; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000648:ultrastructure; D009119:Muscle Contraction; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D009210:Myofibrils / Q000378:metabolism* / Q000648:ultrastructure; D055435:Myostatin / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress
D015415:Biomarkers; C525912:Mstn protein, mouse; D055435:Myostatin; D002950:Citrate (si)-Synthase