Novel mechanisms of Muscle maturation by proteolytic turnover of mTORC1 downstream Lysosomal Phosphoinositide signaling (MuscLY) – MuscLY

The lysosome is a signaling controller hub implicated in virtually every aspect of cellular physiology. Among myriad of assigned processes, a special attention was given to the master growth signaling pathway: mTORC1. Under stimulation, this multimeric complex is assembled and activated on the lysosome. Emerging evidence point to the ubiquitin proteasome system/UPS (a degradation system) as a molecular rheostat in reshaping and adapting the LY to nutrient inputs, however the underlying molecular events emanating from the LY to trigger the UPS-mediated degradation of mTORC1 and the physiological relevance of this crosstalk are still obscure. Here we identified a class of lipids called phosphoinositides, on the Lysosome that trigger the degradation of mTORC1 by UPS. The MuscLY project aims to characterize the relevance of this new mechanism during myogenesis and skeletal muscle maintenance as well as the pathophysiological consequences of their dysfunction in muscle diseases.