Regulating lysosomal composition and function
Our work on amino acid sensing places the lysosome upstream of mTORC1 and of the many anabolic and catabolic processes that mTORC1 controls. For instance, acting via mTORC1, amino acids govern the activity of a family of transcription factors, the MiT/TFE factors, which function as master regulator of lysosomal biogenesis and autophagy. This lysosome-to-nucleus signaling mechanism, which connects the lysosome’s internal status to catabolic gene expression programs, may be the ‘tip of the iceberg’ of a vast regulatory network for metabolic adaptation. To further explore this network, we will investigate how candidate mTORC1 effectors, which we recently identified, control key properties of lysosomes, including their formation, trafficking and their ability to communicate and exchange nutrients with other organelles.