RRC ID 53369
著者 Chen HD, Kao CY, Liu BY, Huang SW, Kuo CJ, Ruan JW, Lin YH, Huang CR, Chen YH, Wang HD, Aroian RV, Chen CS.
タイトル HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans.
ジャーナル Autophagy
Abstract Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we reveal that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans. These results demonstrate that autophagic pathways and autophagy are induced partly at the transcriptional level through HLH-30 activation and are required to protect metazoan upon PFT intoxication. Together, our data show a new and powerful connection between HLH-30-mediated autophagy and epithelium intrinsic cellular defense against the single most common mode of bacterial attack in vivo.
巻・号 13(2)
ページ 371-385
公開日 2017-2-1
DOI 10.1080/15548627.2016.1256933
PMID 27875098
PMC PMC5324838
MeSH Animals Autophagy* / drug effects Autophagy-Related Proteins / genetics Autophagy-Related Proteins / metabolism Bacillus thuringiensis Toxins Bacterial Proteins / toxicity* Base Sequence Basic Helix-Loop-Helix Transcription Factors / metabolism* Caenorhabditis elegans / cytology* Caenorhabditis elegans / drug effects Caenorhabditis elegans / metabolism Caenorhabditis elegans / microbiology* Caenorhabditis elegans Proteins / metabolism* Endotoxins / toxicity* Epithelium / drug effects Epithelium / metabolism* Epithelium / ultrastructure Gene Expression Regulation / drug effects Hemolysin Proteins / toxicity* Intestines / microbiology Intestines / pathology Models, Biological Transcription, Genetic / drug effects
IF 9.77
引用数 12
リソース情報
線虫 tm4364 tm3948 tm287 tm1978 tm4063 tm3949