TFEB and TFE3: Linking Lysosomes to Cellular Adaptation to Stress.
In recent years, our vision of lysosomes has drastically changed. Formerly considered to be mere degradative compartments, they are now recognized as key players in many cellular processes. The ability of lysosomes to respond to different stimuli revealed a complex and coordinated regulation of lysosomal gene expression. This review discusses the participation of the transcription factors TFEB and TFE3 in the regulation of lysosomal function and biogenesis, as well as the role of the lysosomal pathway in cellular adaptation to a variety of stress conditions, including nutrient deprivation, mitochondrial dysfunction, protein misfolding, and pathogen infection. We also describe how cancer cells make use of TFEB and TFE3 to promote their own survival and highlight the potential of these transcription factors as therapeutic targets for the treatment of neurological and lysosomal diseases.
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892; email: rabenn@mail.nih.gov.
Nina
N
Raben
Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; email: puertolr@mail.nih.gov.
Rosa
R
Puertollano
D000222:Adaptation, Physiological; D000818:Animals; D001343:Autophagy / Q000235:genetics; D004734:Energy Metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism*
D014157:Transcription Factors
TFE3; TFEB; autophagy; lysosomes; mTOR; stress