title: The Lysosome as a Regulatory Hub.
abstract: The lysosome has long been viewed as the recycling center of the cell. However, recent discoveries have challenged this simple view and have established a central role of the lysosome in nutrient-dependent signal transduction. The degradative role of the lysosome and its newly discovered signaling functions are not in conflict but rather cooperate extensively to mediate fundamental cellular activities such as nutrient sensing, metabolic adaptation, and quality control of proteins and organelles. Moreover, lysosome-based signaling and degradation are subject to reciprocal regulation. Transcriptional programs of increasing complexity control the biogenesis, composition, and abundance of lysosomes and fine-tune their activity to match the evolving needs of the cell. Alterations in these essential activities are, not surprisingly, central to the pathophysiology of an ever-expanding spectrum of conditions, including storage disorders, neurodegenerative diseases, and cancer. Thus, unraveling the functions of this fascinating organelle will contribute to our understanding of the fundamental logic of metabolic organization and will point to novel therapeutic avenues in several human diseases.
authors: Department of Anatomy and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143; email: rushika.perera@ucsf.edu.
authors: Rushika M
authors: RM
authors: Perera
authors: Department of Molecular and Cellular Biology and Paul F. Glenn Center for Aging Research, University of California, Berkeley, California 94720; email: rzoncu@berkeley.edu.
authors: Roberto
authors: R
authors: Zoncu
mesh_terms: D000818:Animals; D004194:Disease; D005089:Exocytosis; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D015398:Signal Transduction
keywords: TFEB; autophagy; cancer metabolism; lysosomal adaptation; mTORC1; neurodegeneration; nutrient sensing