This study aimed to evaluate the modulatory effect of dietary taurine supplementation on protein turnover of meagre juveniles fed semi-purified plant-based diets. For that purpose, fish (3.2 +/- 0.2 g) were fed with five isoproteic (61.2%), isolipidic (16.6%) and isoenergetic (21.9 kJ g(-1)) experimental diets supplemented with 0.5% (Tau0.5), 1% (Tau1), 1.5% (Tau1.5) and 2% (Tau2) taurine or not (Tau0) for 38 days. The resulting growth parameters, protein expression levels and the activity of several proteolytic markers involved in the two major degradation pathways in vertebrates (autophagy-lysosomal and ubiquitin-proteasome) were assessed in the liver, intestine and white muscle of meagre. Increasing dietary taurine concentrations promoted fish growth, feed utilization and whole-body protein, lipid and energy contents. Dietary taurine seemed to modulate the activity of cathepsins D and B in white muscle and cathepsin L in the liver. Although, no significant effects were observed on proteasome activity, 1% dietary taurine supplementation decreased the expression of the Psmb4 proteasome subunit in the liver of fish when compared to lower taurine concentrations. No taurine effects were detected on the proteolytic markers analysed in the intestine of meagre. Hsp70 expression levels were also not affected by any of the experimental dietary taurine concentrations. Overall, experimental diet Tau2 promoted the highest growth rate which can be explained by a significant decrease in protein degradation in the liver and white muscle preferentially via the autophagy-lysosomal pathway (cathepsins) over the ubiquitin-proteasome route.

Endoplasmic reticulum (ER) stress has been shown to promote chondrocyte apoptosis and osteoarthritis (OA) progression, but the precise mechanisms via which ER stress is modulated in OA remain unclear. Here we report that DEP domain-containing mTOR-interacting protein (DEPTOR) negatively regulated ER stress and OA development independent of mTOR signaling. DEPTOR is ubiquitinated in articular chondrocytes and its expression is markedly reduced along with OA progression. Deletion of DEPTOR in chondrocytes significantly promoted destabilized medial meniscus (DMM) surgery-induced OA development, whereas intra-articular injection of lentivirus-expressing DEPTOR delayed OA progression in mice. Proteomics analysis revealed that DEPTOR interplayed with TRC8, which promoted TRC8 auto-ubiquitination and degraded by the ubiquitin-proteasome system (UPS) in chondrocytes. Loss of DEPTOR led to TRC8 accumulation and excessive ER stress, with subsequent chondrocyte apoptosis and OA progression. Importantly, an inhibitor of ER stress eliminated chondrocyte DEPTOR deletion-exacerbated OA in mice. Together, these findings establish a novel mechanism essential for OA pathogenesis, where decreasing DEPTOR in chondrocytes during OA progression relieves the auto-ubiquitination of TRC8, resulting in TRC8 accumulation, excessive ER stress, and OA progression. Targeting this pathway has promising therapeutic potential for OA treatment. (c) 2020 American Society for Bone and Mineral Research (ASBMR).