Organelles in metabolism and stress responses

Ferguson, Shawn M.; Henne, W. Mike

Lysosomes have attracted considerable attention in recent years due to the growing recognition that their long-appreciated degradative functions are closely coupled with multiple aspects of cell metabolism and regulation of cell growth. Shawn Ferguson (Yale University) explored the mechanisms whereby lysosomes coordinate cellular responses to changes in nutrient availability. This was highlighted by new insights into how a protein complex containing the C9orf72, SMCR8, and WDR41 proteins is recruited to lysosomes to support both the degradative activities of lysosomes and the activation of mTORC1 signaling by intracellular amino acids. Meanwhile, Rose Willett (Puertollano lab, National Institutes of Health) discussed a novel mechanism centered around lysosomal transmembrane protein TMEM55B that regulates lysosome positioning in response to a variety of cellular stress conditions. In response to starvation, the transcription factors TFEB and TFE3 up-regulate TMEM55B expression, promoting JIP4 recruitment and dynein-dependent transport of lysosomes toward the cell center. This pathway was shown to be critical for efficient autophagosome–lysosome fusion.