NDLI: LAMTOR1 depletion induces p53-dependent apoptosis via aberrant lysosomal activation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Malek, M. Guillaumot, P. Huber, A-L Lebeau, J. Pétrilli, V. Kfoury, A. Mikaelian, I. Renno, T. Manié, S. N.
Description	Country affiliation: France Author Affiliation: Malek M ( Université de Lyon, Lyon F-69000, France.)
Abstract	Lysosomal regulation is a poorly understood mechanism that is central to degradation and recycling processes. Here we report that LAMTOR1 (late endosomal/lysosomal adaptor, MAPK and mTOR activator 1) downregulation affects lysosomal activation, through mechanisms that are not solely due to mTORC1 inhibition. LAMTOR1 depletion strongly increases lysosomal structures that display a scattered intracellular positioning. Despite their altered positioning, those dispersed structures remain overall functional: (i) the trafficking and maturation of the lysosomal enzyme cathepsin B is not altered; (ii) the autophagic flux, ending up in the degradation of autophagic substrate inside lysosomes, is stimulated. Consequently, LAMTOR1-depleted cells face an aberrant lysosomal catabolism that produces excessive reactive oxygen species (ROS). ROS accumulation in turn triggers p53-dependent cell cycle arrest and apoptosis. Both mTORC1 activity and the stimulated autophagy are not necessary to this lysosomal cell death pathway. Thus, LAMTOR1 expression affects the tuning of lysosomal activation that can lead to p53-dependent apoptosis through excessive catabolism.
File Format	HTM / HTML
e-ISSN	20414889
DOI	10.1038/cddis.2012.39
Journal	Cell Death and Disease
Volume Number	3
Language	English
Publisher	Nature Publishing Group
Publisher Date	2012-04-19
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Research Support, Non-u.s. Gov't Tor Serine-threonine Kinases Reactive Oxygen Species Rna, Small Interfering Lysosomes Metabolism Autophagy Rna Interference Discipline Cell Biology Cell Cycle Checkpoints Tumor Suppressor Protein P53 Cathepsin B Cell Line, Tumor Genetics Enzymology Apoptosis Carrier Proteins
Content Type	Text
Resource Type	Article

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