Monitoring Autophagy under Cholesterol Starvation in Caenorhabditis elegans

GASTÓN PREZ; DIEGO DE MENDOZA; CATALINA DONSANTI; GUILLERMO LABADIE; CELINA GALLES; EXEQUIEL PORTA

Buenos Aires

Conferencia; Research Conferences on Autophagy; 2017

Universidad de Buenos Aires

In the nematode C. elegans, autophagy genes are essential for the alternative dauer developmental life cycle to take place. These animals are cholesterol auxotrophs and use this sterol as a precursor for dafachronic acid, the hormone whose production prevents dauer formation. We have recently described how endocannabinoids (ECs) modulate intra-cellular cholesterol transport and thus regulate the worm?s life cycle. Here, we set out to determine if cholesterol starvation induces autophagy in C. elegans and if this process is modulated by ECs. We initially determined that first generation daf-2(e1370) nematodes (mutant in the nematode?s sole orthologue of the insulin receptor) grown in sterol-deprived conditions at 20º C experiment a sharp increase in dauer formation. We next established that addition of C18-2- monoacyglycerol ECs is sufficient to revert this developmental arrest. Finally, based on preliminary results indicating a rise in the autophagic flux under cholesterol deprivation, we are currently assaying whether C18-ECs are capable of counteracting this effect.