title: Dialogue between E. coli free radical pathways and the mitochondria of C. elegans.
abstract: The microbial world presents a complex palette of opportunities and dangers to animals, which have developed surveillance and response strategies to hints of microbial intent. We show here that the mitochondrial homeostatic response pathway of the nematode Caenorhabditis elegans responds to Escherichia coli mutations that activate free radical detoxification pathways. Activation of C. elegans mitochondrial responses could be suppressed by additional mutations in E. coli, suggesting that C. elegans responds to products of E. coli to anticipate challenges to its mitochondrion. Out of 50 C. elegans gene inactivations known to mediate mitochondrial defense, we found that 7 genes were required for C. elegans response to a free radical producing E. coli mutant, including the bZip transcription factor atfs-1 (activating transcription factor associated with stress). An atfs-1 loss-of-function mutant was partially resistant to the effects of free radical-producing E. coli mutant, but a constitutively active atfs-1 mutant growing on wild-type E. coli inappropriately activated the pattern of mitochondrial responses normally induced by an E. coli free radical pathway mutant. Carbonylated proteins from free radical-producing E. coli mutant may directly activate the ATFS-1/bZIP transcription factor to induce mitochondrial stress response: feeding C. elegans with H2O2-treated E. coli induces the mitochondrial unfolded protein response, and inhibition of a gut peptide transporter partially suppressed C. elegans response to free radical damaged E. coli.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02115;
authors.forename: J Amaranath
authors.initials: JA
authors.lastname: Govindan
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903.
authors.forename: Elamparithi
authors.initials: E
authors.lastname: Jayamani
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114;
authors.forename: Xinrui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02903.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114; Department of Genetics, Harvard Medical School, Boston, MA 02115; ruvkun@molbio.mgh.harvard.edu.
authors.forename: Gary
authors.initials: G
authors.lastname: Ruvkun
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D053898:Biosynthetic Pathways / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005609:Free Radicals / Q000378:metabolism*; D015870:Gene Expression; D054884:Host-Pathogen Interactions / Q000235:genetics; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C548052:ATFS-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D005609:Free Radicals; D014157:Transcription Factors
keywords: C. elegans; host–microbe dialogue; mitochondria