Signals from the lysosome: a control centre for cellular clearance and energy metabolism

As well as degrading and recycling cellular waste, lysosomes are involved in secretion, plasma membrane repair, signalling and energy metabolism. The identification of transcription factor EB (TFEB) as a central regulator of lysosomal biogenesis and autophagy provides insight into how lysosomes adapt to environmental cues, and targeting TFEB may be a promising therapeutic strategy for modulating lysosomal function in disease. For a long time, lysosomes were considered merely to be cellular 'incinerators' involved in the degradation and recycling of cellular waste. However, now there is compelling evidence indicating that lysosomes have a much broader function and that they are involved in fundamental processes such as secretion, plasma membrane repair, signalling and energy metabolism. Furthermore, the essential role of lysosomes in autophagic pathways puts these organelles at the crossroads of several cellular processes, with significant implications for health and disease. The identification of a master regulator, transcription factor EB (TFEB), that regulates lysosomal biogenesis and autophagy has revealed how the lysosome adapts to environmental cues, such as starvation, and targeting TFEB may provide a novel therapeutic strategy for modulating lysosomal function in human disease.