Absence of Parkin Results in Atrophy of Oxidative Myofibers and Modulation of AKT and MURF1 Signaling in Middle-Aged Male Mice.

AIM: This work aimed to investigate the effects of the loss of Parkin in middle-aged mice skeletal muscle, focusing on different types of myofibers and in the analysis of proteins related to protein synthesis and degradation as well as the analysis of force generation and motor balance. METHODS: We used male mice C57BL/6J (WT) and Parkin knockout mice, Parkintm1Shn (Parkin(-/-)) at 3 and 10 months of age. We used Walking Beam, Open Field, Spider Mice and Maximum Power Tests to assess motor, balance, and endurance functions. We used flexor digitorum brevis (FDB) muscle for force generation analysis, and tibial anterior (TA) and soleus (SOL) muscles were used for biomolecular techniques because of their difference in fiber type. These muscles were used to investigate markers of protein synthesis and degradation, mitochondrial respiration, and myofiber diameter. RESULTS: The Absence of Parkin in middle-aged mice leads to a reduction in isometric force generation but maintained overall motor and locomotion abilities, exhibited only minor balance deficits. In the SOL muscle of middle-aged Parkin(-/-) mice, we observed a reduction of muscle mass and myofiber diameter, also a significant decrease in mitochondrial respiratory capacity and Complex V. In the same group, we observed a reduction in the phosphorylation of AKT and 4E-BP1, and an increase in MURF-1 while Ubiquitin K63 levels decreased. We did not observe relevant differences in the TA muscle. CONCLUSION: Our results suggest middle-aged Parkin(-/-) mice exhibited muscle atrophy and mitochondrial dysfunction primarily in oxidative myofibers before noticeable motor dysfunction occurs.