Olfaction regulates peripheral mitophagy and mitochondrial function.

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.