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

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Article number11726
JournalNature communications
Volume7
DOIs
Publication statusPublished - 2016 May 24

Fingerprint

Autophagy
bacteria
Bacteria
proteins
intestines
Mitochondria
mitochondria
epithelium
infectious diseases
cells
Lipopolysaccharides
induction
depletion
Proteins
Lipoylation
degradation
Degradation
Bacterial Load
Intestinal Mucosa
Cytomegalovirus

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Ra, E. A., Lee, T. A., Won Kim, S., Park, A., Choi, H. J., Jang, I., ... Park, B. (2016). TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells. Nature communications, 7, [11726]. https://doi.org/10.1038/ncomms11726
Ra, Eun A. ; Lee, Taeyun A. ; Won Kim, Seung ; Park, Areum ; Choi, Hyun Jin ; Jang, Insook ; Kang, Sujin ; Hee Cheon, Jae ; Cho, Jin Won ; Eun Lee, Ji ; Lee, Sungwook ; Park, Boyoun. / TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells. In: Nature communications. 2016 ; Vol. 7.
@article{0feda170859d46dbb8705ec126cef959,
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.",
author = "Ra, {Eun A.} and Lee, {Taeyun A.} and {Won Kim}, Seung and Areum Park and Choi, {Hyun Jin} and Insook Jang and Sujin Kang and {Hee Cheon}, Jae and Cho, {Jin Won} and {Eun Lee}, Ji and Sungwook Lee and Boyoun Park",
year = "2016",
month = "5",
day = "24",
doi = "10.1038/ncomms11726",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

Ra, EA, Lee, TA, Won Kim, S, Park, A, Choi, HJ, Jang, I, Kang, S, Hee Cheon, J, Cho, JW, Eun Lee, J, Lee, S & Park, B 2016, 'TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells', Nature communications, vol. 7, 11726. https://doi.org/10.1038/ncomms11726

TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells. / Ra, Eun A.; Lee, Taeyun A.; Won Kim, Seung; Park, Areum; Choi, Hyun Jin; Jang, Insook; Kang, Sujin; Hee Cheon, Jae; Cho, Jin Won; Eun Lee, Ji; Lee, Sungwook; Park, Boyoun.

In: Nature communications, Vol. 7, 11726, 24.05.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells

AU - Ra, Eun A.

AU - Lee, Taeyun A.

AU - Won Kim, Seung

AU - Park, Areum

AU - Choi, Hyun Jin

AU - Jang, Insook

AU - Kang, Sujin

AU - Hee Cheon, Jae

AU - Cho, Jin Won

AU - Eun Lee, Ji

AU - Lee, Sungwook

AU - Park, Boyoun

PY - 2016/5/24

Y1 - 2016/5/24

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84969983820&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84969983820&partnerID=8YFLogxK

U2 - 10.1038/ncomms11726

DO - 10.1038/ncomms11726

M3 - Article

C2 - 27216961

AN - SCOPUS:84969983820

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 11726

ER -

Ra EA, Lee TA, Won Kim S, Park A, Choi HJ, Jang I et al. TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells. Nature communications. 2016 May 24;7. 11726. https://doi.org/10.1038/ncomms11726