title: TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells.
abstract: Autophagy is responsible for the bulk degradation of cytosolic constituents and plays an essential role in the intestinal epithelium by controlling beneficial host-bacterial relationships. Atg5 and Atg7 are thought to be critical for autophagy. However, Atg5- or Atg7-deficient cells still form autophagosomes and autolysosomes, and are capable of removing proteins or bacteria. Here, we report that human TRIM31 (tripartite motif), an intestine-specific protein localized in mitochondria, is essential for promoting lipopolysaccharide-induced Atg5/Atg7-independent autophagy. TRIM31 directly interacts with phosphatidylethanolamine in a palmitoylation-dependent manner, leading to induction of autolysosome formation. Depletion of endogenous TRIM31 significantly increases the number of intestinal epithelial cells containing invasive bacteria. Crohn's disease patients display TRIM31 downregulation. Human cytomegalovirus-infected intestinal cells show a decrease in TRIM31 expression as well as a significant increase in bacterial load, reversible by the introduction of wild-type TRIM31. We provide insight into an alternative autophagy pathway that protects against intestinal pathogenic bacterial infection.
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
authors.forename: Eun A
authors.initials: EA
authors.lastname: Ra
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
authors.forename: Taeyun A
authors.initials: TA
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, South Korea.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, South Korea.
authors.forename: Seung
authors.initials: S
authors.lastname: Won Kim
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
authors.forename: Areum
authors.initials: A
authors.lastname: Park
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Integrated OMICS for Biomedical Science, Yonsei University, Seoul 03722, South Korea.
authors.forename: Insook
authors.initials: I
authors.lastname: Jang
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, South Korea.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, South Korea.
authors.forename: Jae
authors.initials: J
authors.lastname: Hee Cheon
authors.affiliation: Department of Integrated OMICS for Biomedical Science, Yonsei University, Seoul 03722, South Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Cho
authors.affiliation: Department of Health Science and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, South Korea.|Samsung Genome Institute (SGI), Samsung Medical Center, Seoul 06351, South Korea.
authors.forename: Ji
authors.initials: J
authors.lastname: Eun Lee
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
authors.forename: Sungwook
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
authors.forename: Boyoun
authors.initials: B
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D000071187:Autophagy-Related Protein 5 / Q000235:genetics / Q000378:metabolism; D000071193:Autophagy-Related Protein 7 / Q000235:genetics / Q000378:metabolism; D058491:Bacterial Load; D003106:Colon / Q000382:microbiology / Q000473:pathology; D003424:Crohn Disease / Q000382:microbiology / Q000473:pathology*; D003587:Cytomegalovirus; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology; D005260:Female; D055786:Gene Knockout Techniques; D006801:Humans; D007082:Ileum / Q000382:microbiology / Q000473:pathology; D007413:Intestinal Mucosa / Q000166:cytology / Q000382:microbiology / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008247:Lysosomes / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012763:Shigella flexneri; D000070584:Tripartite Motif Proteins / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000502:physiology*; D055815:Young Adult
chemical_list: C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D008070:Lipopolysaccharides; D010714:Phosphatidylethanolamines; D034741:RNA, Small Interfering; D000070584:Tripartite Motif Proteins; C483858:phosphatidylethanolamine; C534233:TRIM31 protein, human; D044767:Ubiquitin-Protein Ligases; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7