Neuronal mitochondrial dynamics coordinate systemic mitochondrial morphology and stress response to confer pathogen resistance in C.elegans.

Abstract

Mitochondrial functions across different tissues are regulated in a coordinated fashion to optimize the fitness of an organism. Mitochondrial unfolded protein response (UPRmt) can be nonautonomously elicited by mitochondrial perturbation in neurons, but neuronal signals that propagate such response and its physiological significance remain incompletely understood. Here, we show that in C.elegans, loss of neuronal fzo-1/mitofusin induces nonautonomous UPRmt through multiple neurotransmitters and neurohormones, including acetylcholine, serotonin, glutamate, tyramine, and insulin-like peptides. Neuronal fzo-1 depletion also triggers nonautonomous mitochondrial fragmentation, which requires autophagy and mitophagy genes. Systemic activation of UPRmt and mitochondrial fragmentation in C.elegans via perturbing neuronal mitochondrial dynamics improves resistance to pathogenic Pseudomonas infection, which is supported by transcriptomic signatures of immunity and stress-response genes. We propose that C.elegans surveils neuronal mitochondrial dynamics to coordinate systemic UPRmt and mitochondrial connectivity for pathogen defense and optimized survival under bacterial infection.