Mitochondrial chaperone HSP‐60 regulates anti‐bacterial immunity via p38 MAP kinase signaling. (10th March 2017)

• Record Type: Journal Article
• Authors: Jeong, Dae‐Eun; Lee, Dongyeop; Hwang, Sun‐Young; Lee, Yujin; Lee, Jee‐Eun; Seo, Mihwa; Hwang, Wooseon; Seo, Keunhee; Hwang, Ara B; Artan, Murat; Son, Heehwa G; Jo, Jay‐Hyun; Baek, Haeshim; Oh, Young Min; Ryu, Youngjae; Kim, Hyung‐Jun; Ha, Chang Man; Yoo, Joo‐Yeon; Lee, Seung‐Jae V
• Is Part Of: EMBO journal. Volume 36:Number 8(2017)
• Page Start: 1046
• Page End: 1065
• Publication Date: 2017-03-10
• Subjects: Caenorhabditis elegans -- HSP‐60 -- mitochondria -- p38 MAP kinase -- Pseudomonas aeruginosa; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201694781
• Languages: English
• ISSNs: 0261-4189

Abstract

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. Synopsis: The chaperone HSP‐60 binds and stabilizes SEK‐1/MAP kinase kinase to regulate p38 MAP kinase activity and anti‐bacterial immunity. Through a large‐scale genetic screen, sixteen mitochondrial components are identified as potential regulators of anti‐bacterial immunity in Caenorhabditis elegans . A fraction of HSP‐60/mitochondrial chaperone is localized in the cytosol and enhances resistance against pathogenic bacteria, Pseudomonas aeruginosa . HSP‐60 up‐regulates cytosolic PMK‐1/p38 MAP kinase signaling through physically interacting with SEK‐1/MAP kinase kinase. Abstract : A Caenorhabditis elegans screen for mitochondrial regulators of cellular immunity reveals that the HSP‐60 chaperone feeds into a conserved anti‐bacterial signaling pathway by stabilizing MKK3/SEK‐1.