title: Aneuploidy triggers a TFEB-mediated lysosomal stress response.
abstract: Aneuploidy, defined as an alteration in chromosome number that is not a multiple of the haploid complement, severely affects cellular physiology. Changes in chromosome number lead to imbalances in cellular protein composition, thus disrupting cellular processes and causing proteins to misfold and aggregate. We recently reported that in mammalian cells protein aggregates are readily encapsulated within autophagosomes but are not degraded by lysosomes. This leads to a lysosomal stress response in which the transcription factor TFEB induces expression of factors needed for macroautophagy-mediated protein degradation. Our studies uncover lysosomal degradation defects as a feature of the aneuploid state, and a role for the transcription factor TFEB in the response thereto.
authors.affiliation: a Koch Institute for Integrative Cancer Research at MIT; Department of Biology; Howard Hughes Medical Institute; Massachusetts Institute of Technology; Cambridge , MA USA.
authors.forename: Stefano
authors.initials: S
authors.lastname: Santaguida
authors.affiliation: a Koch Institute for Integrative Cancer Research at MIT; Department of Biology; Howard Hughes Medical Institute; Massachusetts Institute of Technology; Cambridge , MA USA.
authors.forename: Angelika
authors.initials: A
authors.lastname: Amon
mesh_terms: D000782:Aneuploidy; D001343:Autophagy / Q000235:genetics*; D006801:Humans; D008247:Lysosomes / Q000473:pathology*; D013312:Stress, Physiological / Q000235:genetics*
keywords: TFEB; aneuploidy; autophagy; cancer; proteotoxicity