TRIMs and Galectins Globally Cooperate and TRIM16 and Galectin-3 Co-direct Autophagy in Endomembrane Damage Homeostasis.
Selective autophagy performs an array of tasks to maintain intracellular homeostasis, sterility, and organellar and cellular functionality. The fidelity of these processes depends on precise target recognition and limited activation of the autophagy apparatus in a localized fashion. Here we describe cooperation in such processes between the TRIM family and Galectin family of proteins. TRIMs, which are E3 ubiquitin ligases, displayed propensity to associate with Galectins. One specific TRIM, TRIM16, interacted with Galectin-3 in a ULK1-dependent manner. TRIM16, through integration of Galectin- and ubiquitin-based processes, coordinated recognition of membrane damage with mobilization of the core autophagy regulators ATG16L1, ULK1, and Beclin 1 in response to damaged endomembranes. TRIM16 affected mTOR, interacted with TFEB, and influenced TFEB's nuclear translocation. The cooperation between TRIM16 and Galectin-3 in targeting and activation of selective autophagy protects cells from lysosomal damage and Mycobacterium tuberculosis invasion.
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Northeast, Albuquerque, NM 87131, USA.
Santosh
S
Chauhan
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Northeast, Albuquerque, NM 87131, USA.
Suresh
S
Kumar
Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø - The Arctic University of Norway, 9037 Tromsø, Norway.
Ashish
A
Jain
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Northeast, Albuquerque, NM 87131, USA; Department of Microbiology, Faculty of Science, Mahidol University, 272 Rama VI, Rachathewi, Bangkok 10400, Thailand.
Marisa
M
Ponpuak
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Northeast, Albuquerque, NM 87131, USA.
Michal H
MH
Mudd
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Northeast, Albuquerque, NM 87131, USA.
Tomonori
T
Kimura
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Northeast, Albuquerque, NM 87131, USA.
Seong Won
SW
Choi
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Northeast, Albuquerque, NM 87131, USA.
Ryan
R
Peters
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Northeast, Albuquerque, NM 87131, USA.
Michael
M
Mandell
Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø - The Arctic University of Norway, 9037 Tromsø, Norway.
Jack-Ansgar
JA
Bruun
Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø - The Arctic University of Norway, 9037 Tromsø, Norway. Electronic address: terje.johansen@uit.no.
Terje
T
Johansen
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, Northeast, Albuquerque, NM 87131, USA. Electronic address: vderetic@salud.unm.edu.
Vojo
V
Deretic
D000818:Animals; D001343:Autophagy; D000071189:Autophagy-Related Protein-1 Homolog / Q000378:metabolism; D000071183:Autophagy-Related Proteins / Q000378:metabolism; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D000071186:Beclin-1 / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D019610:Cytoprotection; D004268:DNA-Binding Proteins / Q000378:metabolism*; D037502:Galectin 3 / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000502:physiology; D010766:Phosphorylation; D011485:Protein Binding; D055550:Protein Stability; D000067996:RAW 264.7 Cells; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination
C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; C491997:BECN1 protein, human; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D000071186:Beclin-1; D004268:DNA-Binding Proteins; D037502:Galectin 3; D047908:Intracellular Signaling Peptides and Proteins; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; C064972:TFEB protein, human; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; C117731:TRIM16 protein, human; D044767:Ubiquitin-Protein Ligases; D000071189:Autophagy-Related Protein-1 Homolog; D058570:TOR Serine-Threonine Kinases; C484754:ULK1 protein, human; D019703:Calcineurin
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