title: Galectins and TRIMs directly interact and orchestrate autophagic response to endomembrane damage.
abstract: Macroautophagy/autophagy is a homeostatic process delivering cytoplasmic targets, including damaged organelles, to lysosomes for degradation; however, it is not completely understood how compromised endomembranes are recognized by the autophagic apparatus. We have described previously that the TRIM family of proteins act as receptors for selective autophagy. In this study we uncovered the property of TRIMs to directly interact with members of the family of cytosolic lectins termed galectins. Galectins patrol the cytoplasm and recognize compromised membranes. We show that TRIM16 uses LGALS3 (galectin 3) to detect damaged lysosomes and phagosomes. TRIM16 assembles the core autophagic machinery and is found in protein complexes with MTOR and TFEB, thus regulating their activity to set in motion endomembrane quality control. The TRIM16-LGALS3 system plays a key role in autophagic homeostasis of lysosomes and in the control of Mycobacterium tuberculosis in vivo.
authors.affiliation: a Department of Molecular Genetics and Microbiology , University of New Mexico Health Sciences Center , Northeast , Albuquerque , NM , USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: a Department of Molecular Genetics and Microbiology , University of New Mexico Health Sciences Center , Northeast , Albuquerque , NM , USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Chauhan
authors.affiliation: b Molecular Cancer Research Group , Institute of Medical Biology, University of Tromsø - The Arctic University of Norway , Tromsø , Norway.
authors.forename: Ashish
authors.initials: A
authors.lastname: Jain
authors.affiliation: a Department of Molecular Genetics and Microbiology , University of New Mexico Health Sciences Center , Northeast , Albuquerque , NM , USA.
authors.forename: Marisa
authors.initials: M
authors.lastname: Ponpuak
authors.affiliation: a Department of Molecular Genetics and Microbiology , University of New Mexico Health Sciences Center , Northeast , Albuquerque , NM , USA.
authors.forename: Seong Won
authors.initials: SW
authors.lastname: Choi
authors.affiliation: a Department of Molecular Genetics and Microbiology , University of New Mexico Health Sciences Center , Northeast , Albuquerque , NM , USA.
authors.forename: Michal
authors.initials: M
authors.lastname: Mudd
authors.affiliation: a Department of Molecular Genetics and Microbiology , University of New Mexico Health Sciences Center , Northeast , Albuquerque , NM , USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Peters
authors.affiliation: a Department of Molecular Genetics and Microbiology , University of New Mexico Health Sciences Center , Northeast , Albuquerque , NM , USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mandell
authors.affiliation: b Molecular Cancer Research Group , Institute of Medical Biology, University of Tromsø - The Arctic University of Norway , Tromsø , Norway.
authors.forename: Terje
authors.identifier: http://orcid.org/0000-0003-1451-9578
authors.initials: T
authors.lastname: Johansen
authors.affiliation: a Department of Molecular Genetics and Microbiology , University of New Mexico Health Sciences Center , Northeast , Albuquerque , NM , USA.
authors.forename: Vojo
authors.identifier: http://orcid.org/0000-0002-3624-5208
authors.initials: V
authors.lastname: Deretic
mesh_terms: D000818:Animals; D001343:Autophagy; D011992:Endosomes / Q000378:metabolism*; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D000070584:Tripartite Motif Proteins / Q000378:metabolism*
chemical_list: D037161:Galectins; D000070584:Tripartite Motif Proteins
keywords: TFEB; TOR; lysosome; phagosome; tuberculosis; ubiquitin E3 ligase