A Pilot Study: The Possible Roles Of Exercise-induced Frataxin Expression In Skeletal Muscle

PURPOSE: Mitochondrial protein frataxin (Fxn) is important for the regulation of heme and iron-sulfur clusters (ISC), which are key components for the respiratory chain complexes of mitochondria. However, it is unknown how frataxin plays a role in exercise-induced muscle adaptations. Hence, we conducted a pilot study to explore the effects of exercise training on frataxin and its related molecular systems (heme and ISC) in skeletal muscle. METHODS: Using C57BL/6 J mice (mixed sex; 3-4 months old), we administered voluntary running wheel exercise for 16 weeks (EXC; n = 6). While EXC mice were individually kept in single cages equipped with running wheels, sedentary mice were housed in regular cages without running wheels (CON; n = 5). After exercise training, we conducted molecular analyses (e.g., RT-PCR, colorimetric assay) to determine gene expressions, iron levels, and aconitase activity in skeletal muscles (i.e., tibialis anterior). RESULTS: Following the long-term running exercise, we observed that frataxin (Fxn) gene expression was increased in the skeletal muscle of EXC, as compared to CON (p = 0.0554). Notably, exercise-induced frataxin expression seems to be associated with heme biosynthesis, as gene expression levels of heme anabolism (e.g., ferrochelatase (Fech); p = 0.0836) appeared to increase in the skeletal muscle of EXC, which was significantly correlated with the Fxn expression levels (p < 0.05). However, there were no significant changes in the ISC system (ISC biosynthesis (e.g., Nfs1) and aconitase activity). In addition, no significant differences in non-heme iron levels (i.e., mitochondria and cytosol) were found, although frataxin level is associated with iron status. CONCLUSIONS: This pilot study suggests that exercise training may contribute to heme biosynthesis in skeletal muscle via frataxin. Nevertheless, follow-up studies are warranted to further understand the roles of frataxin on the heme system, as well as mitochondrial capacity in exercise-induced muscle adaptations.