RRC ID 45772
著者 Kirienko NV, Ausubel FM, Ruvkun G.
タイトル Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa.
ジャーナル Proc Natl Acad Sci U S A
Abstract In the arms race of bacterial pathogenesis, bacteria produce an array of toxins and virulence factors that disrupt core host processes. Hosts mitigate the ensuing damage by responding with immune countermeasures. The iron-binding siderophore pyoverdin is a key virulence mediator of the human pathogen Pseudomonas aeruginosa, but its pathogenic mechanism has not been established. Here we demonstrate that pyoverdin enters Caenorhabditis elegans and that it is sufficient to mediate host killing. Moreover, we show that iron chelation disrupts mitochondrial homeostasis and triggers mitophagy both in C. elegans and mammalian cells. Finally, we show that mitophagy provides protection both against the extracellular pathogen P. aeruginosa and to treatment with a xenobiotic chelator, phenanthroline, in C. elegans. Although autophagic machinery has been shown to target intracellular bacteria for degradation (a process known as xenophagy), our report establishes a role for authentic mitochondrial autophagy in the innate immune defense against P. aeruginosa.
巻・号 112(6)
ページ 1821-6
公開日 2015-2-10
DOI 10.1073/pnas.1424954112
PII 1424954112
PMID 25624506
PMC PMC4330731
MeSH Animals Caenorhabditis elegans Fluorescence HEK293 Cells Homeostasis / drug effects* Humans Immunity, Innate / immunology* Iron / metabolism Microscopy, Confocal Mitophagy / drug effects* Mitophagy / immunology Oligopeptides / metabolism Oligopeptides / toxicity* Phenanthrolines Pseudomonas aeruginosa / metabolism* Siderophores / metabolism Siderophores / toxicity*
IF 9.412
引用数 82
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm1779 tm4248