Figure 3.

The lysosome as a regulator of lipid metabolism. In the fed state (upper panel), the presence of lysosomal amino acids (AA), glucose, and growth factors induces activation of mechanistic target of rapamycin complex 1 (mTORC1) on the lysosomal membrane. Active mTORC1 transcriptionally induces lipogenesis and adipogenesis by activating SREBPs and peroxisome proliferator-activated receptor (PPAR)γ transcription factors, respectively. Concomitantly, mTORC1 blocks autophagy and fatty acid oxidation via transcription factor EB (TFEB) and PPARα inhibition, respectively. In the fasted state (lower panel), lower levels of lysosomal AA, glucose, and growth factors induce mTORC1 detachment from the lysosomal membrane and its consequent inhibition. mTORC1 inhibition in turn activates TFEB and PPARα transcription factors, which leads to the transcriptional induction of lipophagy and β-oxidation, respectively. Concomitantly, SREBPs and PPARγ are no longer activated by mTORC1, therefore lipogenesis and adipogenesis are inhibited. Abbreviations: Rheb, Ras homolog enriched in brain; Rags, Ras-related small GTP-binding protein; SREBPs, sterol regulatory element-binding proteins.