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Rpn13 is an intrinsic ubiquitin receptor of the 26S proteasome regulatory subunit that facilitates substrate capture prior to degradation. Here we show that the C-terminal region of Rpn13 binds to the tetratricopeptide repeat (TPR) domain of SGTA, a cytosolic factor implicated in the quality control of mislocalised membrane proteins (MLPs). The overexpression of SGTA results in a substantial increase in steady-state MLP levels, consistent with an effect on proteasomal degradation. However, this effect is strongly dependent upon the interaction of SGTA with the proteasomal component Rpn13. Hence, overexpression of the SGTA-binding region of Rpn13 or point mutations within the SGTA TPR domain both inhibit SGTA binding to the proteasome and substantially reduce MLP levels. These findings suggest that SGTA can regulate the access of MLPs to the proteolytic core of the proteasome, implying that a protein quality control cycle that involves SGTA and the BAG6 complex can operate at the 19S regulatory particle. We speculate that the binding of SGTA to Rpn13 enables specific polypeptides to escape proteasomal degradation and/or selectively modulates substrate degradation.
Many sports employ caloric restriction (CR) to reduce athletes’ body mass. During these phases, resistance training (RT) volume is often reduced to accommodate recovery demands. Since RT volume is a well-known anabolic stimulus, this review investigates whether a higher training volume helps to spare lean mass during CR. A total of 15 studies met inclusion criteria. The extracted data allowed calculation of total tonnage lifted (repetitions × sets × intensity load) or weekly sets per muscle group for only 4 of the 15 studies, with RT volume being highly dependent on the examined muscle group as well as weekly training frequency per muscle group. Studies involving high RT volume programs (≥ 10 weekly sets per muscle group) revealed low-to-no (mostly female) lean mass loss. Additionally, studies increasing RT volume during CR over time appeared to demonstrate no-to-low lean mass loss when compared to studies reducing RT volume. Since data regarding RT variables applied were incomplete in most of the included studies, evidence is insufficient to conclude that a higher RT volume is better suited to spare lean mass during CR, although data seem to favor higher volumes in female athletes during CR. Moreover, the data appear to suggest that increasing RT volume during CR over time might be more effective in ameliorating CR-induced atrophy in both male and female resistance-trained athletes when compared to studies reducing RT volume. The effects of CR on lean mass sparing seem to be mediated by training experience, pre-diet volume, and energy deficit, with, on average, women tending to spare more lean mass than men. Potential explanatory mechanisms for enhanced lean mass sparing include a preserved endocrine milieu as well as heightened anabolic signaling.