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

Abstract

Autophagyis responsible for the bulk degradation of cytosolic constituents and plays an essential role in theintestinalepithelium by controlling beneficial host-bacterial relationships.Atg5and Atg7 are thought to be critical forautophagy. However,Atg5- or Atg7-deficientcellsstill form autophagosomes and autolysosomes, and are capable of removing proteins or bacteria. Here, we report that humanTRIM31(tripartite motif), an intestine-specific protein localized in mitochondria, is essential for promoting lipopolysaccharide-inducedAtg5/Atg7-independentautophagy.TRIM31directly interacts with phosphatidylethanolamine in a palmitoylation-dependent manner, leading to induction of autolysosome formation. Depletion of endogenousTRIM31significantly increases the number ofintestinalepithelialcellscontaining invasive bacteria. Crohn's disease patients displayTRIM31downregulation. Human cytomegalovirus-infectedintestinalcellsshow a decrease inTRIM31expression as well as a significant increase in bacterial load, reversible by the introduction of wild-typeTRIM31. We provide insight into an alternativeautophagypathway that protects againstintestinalpathogenic bacterial infection.