Olfaction regulates peripheral mitophagy and mitochondrial function | Science Advances

The central nervous system coordinates peripheral cellular stress responses, including the unfolded protein response of the mitochondria (UPR ^MT ); however, the contexts for which this regulatory capability evolved are unknown. UPR ^MT is up-regulated upon pathogenic infection and in metabolic flux, and the olfactory nervous system has been shown to regulate pathogen resistance and peripheral metabolic activity. Therefore, we asked whether the olfactory nervous system in Caenorhabditis elegans controls the UPR ^MT cell nonautonomously. We found that silencing a single inhibitory olfactory neuron pair, AWC, led to robust induction of UPR ^MT and reduction of oxidative phosphorylation dependent on serotonin signaling and parkin -mediated mitophagy. Further, AWC ablation confers resistance to the pathogenic bacteria Pseudomonas aeruginosa partially dependent on the UPR ^MT transcription factor atfs-1 and fully dependent on mitophagy machinery. These data illustrate a role for the olfactory nervous system in regulating whole-organism mitochondrial dynamics, perhaps in preparation for postprandial metabolic stress or pathogenic infection.