TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells

Eun A Ra; Taeyun A Lee; Seung Won Kim; Areum Park; Hyun Jin Choi; Insook Jang; Sujin Kang; Jae Hee Cheon; Jin Won Cho; Ji Eun Lee; Sungwook Lee; Boyoun Park

doi:10.1038/ncomms11726

TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells

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

Authors

Eun A Ra¹, Taeyun A Lee¹, Seung Won Kim^{2

3}, Areum Park¹, Hyun Jin Choi¹, Insook Jang⁴, Sujin Kang¹, Jae Hee Cheon^{2

3}, Jin Won Cho⁴, Ji Eun Lee^{5

6}, Sungwook Lee¹, Boyoun Park¹

Affiliations

¹ Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
² Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 03722, South Korea.
³ Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, South Korea.
⁴ Department of Integrated OMICS for Biomedical Science, Yonsei University, Seoul 03722, South Korea.
⁵ Department of Health Science and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, South Korea.
⁶ Samsung Genome Institute (SGI), Samsung Medical Center, Seoul 06351, South Korea.

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