Mito-Nuclear Interactions Moderate the Impact of Chloramphenicol on Drosophila Immunometabolism

Abstract

The chimeric bacteria-derived mitochondria govern the cellular flux of metabolites through energy conversion-, biosynthesis- and signalling pathways that constitute the interface between the organismal inside and outside environments. The dynamic coordination of mitochondrial functions depends on intricate interactions between mitochondrial genes encoded by both the cellular nucleus (nDNA), multicopy mitochondrial genomes (mtDNA) and external exposures. Although these interactions clearly influence the manifestation of phenotypes and contribute to the variability of health outcomes, their molecular underpinnings are still scarcely understood. In this project we have screened the impact of the translation-inhibiting antibiotic chloramphenicol on the development of <i>Drosophila melanogaster</i> across a panel of nuclear-mitochondrial cybrid lines. We show that chloramphenicol directly influences <i>Drosophila</i> mitochondrial functions and that its impact <i>in vivo</i> is strongly moderated by interactions between mitochondrial genomes and their nuclear backgrounds. We describe the chloramphenicol-induced activation of a female-biased cellular immune response across multiple mitotypes in the <i>Oregen R</i> nuclear background. We have determined that this response can be rescued by the co-supplementation of the B3 vitamer nicotinamide. Our results further strengthen the causative role of mitochondrial insult for the activation of innate immunity and highlight the impact of mitochondrial genetic variability on the organismal response to stressful stimuli.