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Mitochondrial aconitase suppresses immunity by modulating oxaloacetate and the mitochondrial unfolded protein response.
Kim, Eunah; Annibal, Andrea; Lee, Yujin; Park, Hae-Eun H; Ham, Seokjin; Jeong, Dae-Eun; Kim, Younghun; Park, Sangsoon; Kwon, Sujeong; Jung, Yoonji; Park, JiSoo; Kim, Sieun S; Antebi, Adam; Lee, Seung-Jae V.
Afiliación
  • Kim E; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
  • Annibal A; Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, Cologne, 50931, Germany.
  • Lee Y; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
  • Park HH; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
  • Ham S; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
  • Jeong DE; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, South Korea.
  • Kim Y; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
  • Park S; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
  • Kwon S; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
  • Jung Y; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
  • Park J; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
  • Kim SS; Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, 34141, South Korea.
  • Antebi A; Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, Cologne, 50931, Germany. aantebi@age.mpg.de.
  • Lee SV; Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Cologne, Germany. aantebi@age.mpg.de.
Nat Commun ; 14(1): 3716, 2023 06 22.
Article en En | MEDLINE | ID: mdl-37349299
Accumulating evidence indicates that mitochondria play crucial roles in immunity. However, the role of the mitochondrial Krebs cycle in immunity remains largely unknown, in particular at the organism level. Here we show that mitochondrial aconitase, ACO-2, a Krebs cycle enzyme that catalyzes the conversion of citrate to isocitrate, inhibits immunity against pathogenic bacteria in C. elegans. We find that the genetic inhibition of aco-2 decreases the level of oxaloacetate. This increases the mitochondrial unfolded protein response, subsequently upregulating the transcription factor ATFS-1, which contributes to enhanced immunity against pathogenic bacteria. We show that the genetic inhibition of mammalian ACO2 increases immunity against pathogenic bacteria by modulating the mitochondrial unfolded protein response and oxaloacetate levels in cultured cells. Because mitochondrial aconitase is highly conserved across phyla, a therapeutic strategy targeting ACO2 may eventually help properly control immunity in humans.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aconitato Hidratasa / Caenorhabditis elegans Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aconitato Hidratasa / Caenorhabditis elegans Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Reino Unido