한빛사논문
- 조회411
Eunah Kim 1,5, Andrea Annibal 2,5, Yujin Lee 1,5, Hae-Eun H. Park 1,5, Seokjin Ham 1,5, Dae-Eun Jeong 3, Younghun Kim 1, Sangsoon Park 1,Sujeong Kwon 1, Yoonji Jung 1, JiSoo Park 1, Sieun S. Kim 1, Adam Antebi 2,4,* & Seung-Jae V. Lee 1,*
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, South Korea.
2Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, Cologne 50931, Germany.
3Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea.
4Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
5These authors contributed equally: Eunah Kim, Andrea Annibal, Yujin Lee, Hae-Eun H. Park, Seokjin Ham.
*Corresponding author: correspondence to Adam Antebi or Seung-Jae V. Lee
Abstract
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.
논문정보
- Research article
- 2023년 06월 (BRIC 등록일 2023-06-23)
- 국내(교신)+국외 연구진
- 생명과학 > 노화/암생물학
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