| RRC ID |
80861
|
| Author |
Kim E, Annibal A, Lee Y, Park HH, Ham S, Jeong DE, Kim Y, Park S, Kwon S, Jung Y, Park J, Kim SS, Antebi A, Lee SV.
|
| Title |
Mitochondrial aconitase suppresses immunity by modulating oxaloacetate and the mitochondrial unfolded protein response.
|
| Journal |
Nat Commun
|
| 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.
|
| Volume |
14(1)
|
| Pages |
3716
|
| Published |
2023-6-22
|
| DOI |
10.1038/s41467-023-39393-6
|
| PII |
10.1038/s41467-023-39393-6
|
| PMID |
37349299
|
| PMC |
PMC10287738
|
| MeSH |
Aconitate Hydratase* / genetics
Animals
Caenorhabditis elegans* / genetics
Caenorhabditis elegans* / metabolism
Humans
Mammals / metabolism
Oxaloacetates
Oxaloacetic Acid
Unfolded Protein Response
|
| Resource |
| C.elegans |
tm1817
tm4525
tm3036
tm4067
tm1978 |
