Beschreibung
Dysregulation of lipid metabolism plays an important role in aging and disease, however, microbiome impact on lipid homeostasis and lipid signaling in host-microbe interactions are poorly understood, especially in the context of mitochondrial dysfunction. Mitochondria are endosymbiotic organelles that take part in bidirectional crosstalk with microbiome, in part via lipids, either biotransformed or biosynthesized by the gut microbiome, but the exact mechanisms remain unclear.
We observed a complete repression of longevity in the Caenorhabditis elegans complex III mitochondrial respiratory chain (MRC) mutant deficient in endogenous branched-chain fatty acid (BCFA) synthesis, and this effect could be reversed by growing the nematodes in presence of Bacillus subtilis, in which BCFAs represent more than 80% of the total FAs. Remarkably, B. subtilis mutants in nucleotide metabolism genes failed to reverse the BCFA-deficient-MRC-mutants’ phenotypes. Furthermore, we performed proteomic analyses both on BCFA-deficient worms with and without B. subtilis supplementation and on B. subtilis purB mutant. Multiple enzymes involved in de novo purine synthesis were among the top downregulated proteins in the worms deficient in endogenous BCFAs, and we further confirmed this on a transcript level. Strikingly, the major downregulated proteins in the B. subtilis purB mutant were the ones involved in the synthesis of branched-chain amino acids (BCAAs), which are the known BCFAs precursors both in bacteria and eukaryotes. In summary, our findings reveal a complex interplay between BCFA, BCAA and nucleotide metabolism of the host that can be modulated by its microbiome, and its relevance for organism’s physiology.
| Affiliation | University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne Excellence Cluster for Aging and Aging-Associated Diseases (CECAD) |
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