Neuronal Control Of Mitochondrial Stress Responses And Their Impact On Metabolism
Mitochondrial stress responses are essential molecular mechanisms that maintain homeostasis when an organism is faced with stress. Local stress responses can be communicated to distal tissues to enable global reactions to challenges, thereby increasing the chance of organismal survival. The nervous system is critical for coordinating systemic stress responses, yet the mechanisms by which this is achieved remain largely unknown. Using the model Caenorhabditis elegans, we aim to generate a more holistic understanding of how the nervous system controls distal mitochondrial function and health. We previously showed that the E-twenty-six transcription factor ETS-5 controls intestinal fat storage from pair of head sensory neurons (the BAG neurons). Increased intestinal fat storage in the absence of ETS-5 induces a sleep-like state known as quiescence. As sleep and metabolic alterations are a hallmark of systemic stress responses, the combination of increased fat storage and quiescence in an ets-5 mutant implicates ETS-5 as a potential stress mediator. Our subsequent analysis revealed that ETS-5 indeed controls a highly specific systemic mitochondrial stress response. Furthermore, we found that the BAG neurons utilise several neuropeptide networks – both dependent and independent of ETS-5 – to illicit unique systemic mitochondrial stress responses. These responses have differing effects on organismal health and mitochondrial function, the full effects of which are being deciphered.