ACTN3 and muscle atrophy: Since Actn3 expression levels increased during natural aging process (Fig. 4f, g), we further evaluated whether the ablation of Mib1 leads to dysregulation and accumulation of Actn3 related to protein degradation and induction of other common E3 ubiquitin ligases (Atrogin1 and MuRF) related to muscle atrophy in vivo.