TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells

Nat Commun. 2016 May 24;7:11726. doi: 10.1038/ncomms11726.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autophagy / drug effects
  • Autophagy / physiology*
  • Autophagy-Related Protein 5 / genetics
  • Autophagy-Related Protein 5 / metabolism
  • Autophagy-Related Protein 7 / genetics
  • Autophagy-Related Protein 7 / metabolism
  • Bacterial Load
  • Colon / microbiology
  • Colon / pathology
  • Crohn Disease / microbiology
  • Crohn Disease / pathology*
  • Cytomegalovirus
  • Down-Regulation
  • Epithelial Cells / metabolism*
  • Epithelial Cells / microbiology
  • Female
  • Gene Knockout Techniques
  • Humans
  • Ileum / microbiology
  • Ileum / pathology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / physiology*
  • Lipopolysaccharides / pharmacology
  • Lysosomes / metabolism
  • Lysosomes / microbiology
  • Male
  • Middle Aged
  • Mitochondria / metabolism
  • Phosphatidylethanolamines / metabolism
  • RNA, Small Interfering / metabolism
  • Shigella flexneri
  • Tripartite Motif Proteins / physiology*
  • Ubiquitin-Protein Ligases / physiology*
  • Young Adult

Substances

  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • Lipopolysaccharides
  • Phosphatidylethanolamines
  • RNA, Small Interfering
  • Tripartite Motif Proteins
  • phosphatidylethanolamine
  • TRIM31 protein, human
  • Ubiquitin-Protein Ligases
  • Atg7 protein, human
  • Autophagy-Related Protein 7