Vodickova, Anezka et al. (2021) International Worm Meeting "The impact of perceived and internal metabolic states on behavior and hypoxic responses in C. elegans"

Vodickova, Anezka, Nieves, Tyrone, Wojtovich, Andrew

[International Worm Meeting, 2021]

Caenorhabditis elegans surveil their environment and respond through behavioral changes. One factor that influences behavior is the metabolic state. The energy status can influence worm locomotion behavior to increase chances of finding or staying on a food source. Mitochondria are metabolic hubs of the cell and use oxygen to produce energy. How mitochondrial function alters behavior and hypoxic signaling is unclear. We designed the optogenetic tools mitochondria-ON (mtON) and mitochondria-OFF (mtOFF) to mimic or suppress mitochondrial function. Upon activation with light, these tools can control the energy state in select tissue through the use of tissue-selective promoters. Given that energy-sensing is driven by neurons, and the intestine is responsible for nutrient utilization, light activation of these animals can serve as a model of perceived or internal metabolic state, respectively. We characterized our model and observed a decrease in total ATP levels in response to mtOFF activation in the intestine, with no effect of activation in neurons. The metabolic state can lead to signaling that influences hypoxic responses. Hence, we next examined the response of C. elegans to short-term hypoxic exposures. The regulation of mitochondrial function in C. elegans led to alterations in the periods of recovery from 1-hour hypoxia. Overall, we demonstrate that the tissue-specific reduction of mitochondrial function by mtOFF in the intestine affects whole body ATP production compared to the activation of neuronal mtOFF, where there were no changes in ATP levels between worms with activated and deactivated mtOFF. In conclusion, our optogenetic model allows us to study the effects of modulating mitochondrial function on behavior and metabolic responses.