Leermakers PA, et al. - Since loss of skeletal muscle mitochondrial content was well-established in muscle unloading models, however, the underlying molecular mechanism remains uncertain, researchers tested the assumption that apparent unloading-induced loss of muscle mitochondrial content was preceded by increased mitophagy- and reduced mitochondrial biogenesis-signaling during the early stages of unloading. A comprehensive set of molecular markers were analyzed included in mitochondrial-autophagy, -biogenesis, -dynamics, and -content, in the gastrocnemius muscle of C57BL/6J mice subjected to 0- and 3-days hind limb suspension, and in biopsies from human vastus lateralis muscle collected earlier and after 7-days of one-leg immobilization. According to results, short-term skeletal muscle unloading in both mice and men results in molecular marker patterns that indicate increased receptor-mediated mitophagy and decreased regulation of mitochondrial biogenesis before the apparent loss of mitochondrial content. These outcomes highlight the early onset of mitochondrial remodeling induced by the skeletal muscle disuse.