Lysosomal Adaptation: How the Lysosome Responds to External Cues
- Carmine Settembre1,2,3,4 and
- Andrea Ballabio1,2,3,4
- 1Telethon Institute of Genetics and Medicine, 80131 Naples, Italy
- 2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030
- 3Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, Texas 77030
- 4Medical Genetics, Department of Translational Medicine, Federico II University, 80131 Naples, Italy
- Correspondence: ballabio{at}tigem.it
Abstract
Recent evidence indicates that the importance of the lysosome in cell metabolism and organism physiology goes far beyond the simple disposal of cellular garbage. This dynamic organelle is situated at the crossroad of the most important cellular pathways and is involved in sensing, signaling, and transcriptional mechanisms that respond to environmental cues, such as nutrients. Two main mediators of these lysosomal adaptation mechanisms are the mTORC1 kinase complex and the transcription factor EB (TFEB). These two factors are linked in a lysosome-to-nucleus signaling pathway that provides the lysosome with the ability to adapt to extracellular cues and control its own biogenesis. Modulation of lysosomal function by acting on TFEB has a profound impact on cellular clearance and energy metabolism and is a promising therapeutic target for a large variety of disease conditions.
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