AI Article Synopsis
- Mitochondria are important for immune function, but their specific role in the Krebs cycle, particularly in organisms, is not well understood.
- This study reveals that inhibiting the enzyme mitochondrial aconitase (ACO-2) in C. elegans enhances immunity against bacteria by affecting oxaloacetate levels and triggering a response related to mitochondrial stress.
- Findings suggest that targeting ACO2 may improve immune responses against bacterial pathogens not only in C. elegans but potentially in humans as well, since this enzyme is highly conserved across different species.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10287738 | PMC |
| http://dx.doi.org/10.1038/s41467-023-39393-6 | DOI Listing |
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