RRC ID 51347
Author Jeong DE, Lee D, Hwang SY, Lee Y, Lee JE, Seo M, Hwang W, Seo K, Hwang AB, Artan M, Son HG, Jo JH, Baek H, Oh YM, Ryu Y, Kim HJ, Ha CM, Yoo JY, Lee SV.
Title Mitochondrial chaperone HSP-60 regulates anti-bacterial immunity via p38 MAP kinase signaling.
Journal EMBO J
Abstract Mitochondria play key roles in cellular immunity. How mitochondria contribute to organismal immunity remains poorly understood. Here, we show that HSP-60/HSPD1, a major mitochondrial chaperone, boosts anti-bacterial immunity through the up-regulation of p38 MAP kinase signaling. We first identify 16 evolutionarily conserved mitochondrial components that affect the immunity of Caenorhabditis elegans against pathogenic Pseudomonas aeruginosa (PA14). Among them, the mitochondrial chaperone HSP-60 is necessary and sufficient to increase resistance to PA14. We show that HSP-60 in the intestine and neurons is crucial for the resistance to PA14. We then find that p38 MAP kinase signaling, an evolutionarily conserved anti-bacterial immune pathway, is down-regulated by genetic inhibition of hsp-60, and up-regulated by increased expression of hsp-60 Overexpression of HSPD1, the mammalian ortholog of hsp-60, increases p38 MAP kinase activity in human cells, suggesting an evolutionarily conserved mechanism. Further, cytosol-localized HSP-60 physically binds and stabilizes SEK-1/MAP kinase kinase 3, which in turn up-regulates p38 MAP kinase and increases immunity. Our study suggests that mitochondrial chaperones protect host eukaryotes from pathogenic bacteria by up-regulating cytosolic p38 MAPK signaling.
Volume 36(8)
Pages 1046-1065
Published 2017-4-13
DOI 10.15252/embj.201694781
PII embj.201694781
PMID 28283579
PMC PMC5391144
MeSH Animals Animals, Genetically Modified / genetics Animals, Genetically Modified / immunology Caenorhabditis elegans / genetics Caenorhabditis elegans / immunology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / immunology Chaperonin 60 / genetics Chaperonin 60 / immunology* Humans MAP Kinase Kinase 4 / genetics MAP Kinase Kinase 4 / immunology MAP Kinase Signaling System / genetics MAP Kinase Signaling System / immunology* Mitochondrial Proteins / genetics Mitochondrial Proteins / immunology* Pseudomonas aeruginosa / immunology* p38 Mitogen-Activated Protein Kinases / genetics p38 Mitogen-Activated Protein Kinases / immunology*
IF 9.889
Times Cited 17
C.elegans tm4067