Correction: Muscle health in a mouse model of Duchenne muscular dystrophy can be partially improved by restoring mitochondrial creatine metabolism

Disrupted cardiac bioenergetics linked to oxidized mitochondrial creatine kinase are rescued by the mitochondrial-targeting peptide SBT-20 in the D2.mdx model of Duchenne muscular dystrophy

“…We were unable to assess cardiac function in aged D2.mdx mice due to their qualitatively frail nature. Furthermore, while we did not see robust differences in grip strength compared to agematched wild type mice, we did note that the absolute values of grip strength in the 12 month old wild type mice are ~50% of the values we have reported previously in this strain at 4 weeks of age [7,16] suggesting an aging effect occurred in the control group. Nonetheless, the other parameters demonstrate a severe myopathy in the aged D2.mdx mice.…”

“…The greater abundance of cysteine oxidation on mtCK was consistent with higher rates of creatine-sensitive mH2O2 during oxidative phosphorylation and the more oxidized cellular environment (lower GSH:GSSG). mtCK oxidation may be unique to advanced stages of this disease, given we previously reported no differences in 4-week D2.mdx mice, at least in skeletal muscle [16]. Further studies could examine the precise form of thiol modification that occurs in aged D2.mdx mice, such as glutathionylation, considering its emerging role in linking redox signaling to metabolic control [20,21] and considering the shift in GSH:GSSG noted in the present study.…”

“…Nonetheless, the other parameters demonstrate a severe myopathy in the aged D2.mdx mice. Also, the effect of age on mitochondrial reprogramming in locomotor and respiratory muscle pathology compared to muscle dysfunction could also be considered, particularly in relation to the earlier remodeling seen in 4-week-old D2.mdx [6,7,16,23].…”

“…The increased creatine-dependent mH2O2 during oxidative phosphorylation in aged D2.mdx mice guided us to hypothesize that mtCK thiols would be more oxidized than in wild type given mtCK is a redox-sensitive protein (reviewed in [9]). We next immunoprecipitated mtCK from left ventricles and incubated the extract in a maleimide-tagged fluorophore that binds irreversibly to reduced cysteine thiols, with no affinity to oxidized thiols, as previously described ( [16][17][18], Supplemental Figure S3). This experiment demonstrated that mtCK is more oxidized in aged D2.mdx mice (Figure 3A).…”