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Mitochondrial chaperone HSP ‐60 regulates anti‐bacterial immunity via p38 MAP kinase signaling
Author(s) -
Jeong DaeEun,
Lee Dongyeop,
Hwang SunYoung,
Lee Yujin,
Lee JeeEun,
Seo Mihwa,
Hwang Wooseon,
Seo Keunhee,
Hwang Ara B,
Artan Murat,
Son Heehwa G,
Jo JayHyun,
Baek Haeshim,
Oh Young Min,
Ryu Youngjae,
Kim HyungJun,
Ha Chang Man,
Yoo JooYeon,
Lee SeungJae V
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201694781
Subject(s) - biology , microbiology and biotechnology , caenorhabditis elegans , kinase , p38 mitogen activated protein kinases , cytosol , mitochondrion , signal transduction , chaperone (clinical) , immunity , protein kinase a , immune system , genetics , biochemistry , gene , enzyme , medicine , pathology
Mitochondria play key roles in cellular immunity. How mitochondria contribute to organismal immunity remains poorly understood. Here, we show that HSP ‐60/ HSPD 1, 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 ( PA 14). Among them, the mitochondrial chaperone HSP ‐60 is necessary and sufficient to increase resistance to PA 14. We show that HSP ‐60 in the intestine and neurons is crucial for the resistance to PA 14. 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 HSPD 1 , 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.