title: Mitochondrial chaperone HSP-60 regulates anti-bacterial immunity via p38 MAP kinase signaling.
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 ofCaenorhabditis elegansagainst pathogenicPseudomonas 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 ofhsp-60, and up-regulated by increased expression ofhsp-60Overexpression ofHSPD1, the mammalian ortholog ofhsp-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.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Dae-Eun
authors.initials: DE
authors.lastname: Jeong
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Dongyeop
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Hwang
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Jee-Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Mihwa
authors.initials: M
authors.lastname: Seo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Wooseon
authors.initials: W
authors.lastname: Hwang
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Keunhee
authors.initials: K
authors.lastname: Seo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Ara B
authors.initials: AB
authors.lastname: Hwang
authors.affiliation: Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Murat
authors.initials: M
authors.lastname: Artan
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Heehwa G
authors.initials: HG
authors.lastname: Son
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Jay-Hyun
authors.initials: JH
authors.lastname: Jo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Haeshim
authors.initials: H
authors.lastname: Baek
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Oh
authors.affiliation: Research Division, Korea Brain Research Institute, Daegu, Korea.
authors.forename: Youngjae
authors.initials: Y
authors.lastname: Ryu
authors.affiliation: Research Division, Korea Brain Research Institute, Daegu, Korea.
authors.forename: Hyung-Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Research Division, Korea Brain Research Institute, Daegu, Korea.
authors.forename: Chang Man
authors.initials: CM
authors.lastname: Ha
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea jyoo@postech.ac.kr seungjaelee@postech.ac.kr.
authors.forename: Joo-Yeon
authors.identifier: 0000-0001-5942-3989
authors.initials: JY
authors.lastname: Yoo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea jyoo@postech.ac.kr seungjaelee@postech.ac.kr.|School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.|Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
authors.forename: Seung-Jae V
authors.identifier: 0000-0002-6103-156X
authors.initials: SV
authors.lastname: Lee
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000276:immunology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000276:immunology; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000276:immunology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D018834:Chaperonin 60; D024101:Mitochondrial Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C516679:sek-1 protein, C elegans
keywords: 
  Caenorhabditis elegans
  ; 
  Pseudomonas aeruginosa
  ; HSP‐60; mitochondria; p38 MAP kinase