RESUMO
The links between autophagy and genome stability, and whether they are important for lifespan and health, are not fully understood. We undertook a study to explore this notion at the molecular level using Saccharomyces cerevisiae. On the one hand, we triggered autophagy using rapamycin, to which we exposed mutants defective in preserving genome integrity, then assessed their viability, their ability to induce autophagy and the link between these two parameters. On the other hand, we searched for molecules derived from plant extracts known to have powerful benefits on human health to try to rescue the negative effects rapamycin had against some of these mutants. We uncover that autophagy execution is lethal for mutants unable to repair DNA double strand breaks, while the extract from Silybum marianum seeds induces an expansion of the endoplasmic reticulum (ER) that blocks autophagy and protects them. Our data uncover a connection between genome integrity and homeostasis of the ER whereby ER stress-like scenarios render cells tolerant to sub-optimal genome integrity conditions.
RESUMO
The endoplasmic reticulum (ER) is a central organelle in charge of correct protein folding; lipids synthesis, modification, and sorting; as well as of maintenance of calcium homeostasis. To accomplish these functions, the ER lumen possesses an oxidative potential. Challenging cells with reductive agents therefore provokes an ER stress that immediately affects protein folding, and which morphologically manifests by an expansion of the cytoplasmic ER network. Yet less is known about the impact on the ER of exposing cells to oxidative agents, which risk to exacerbate the basal, physiologically oxidative environment. We have monitored the morphology of the ER of Saccharomyces cerevisiae in response to this type of treatment. We bring the notion that oxidative agents give rise to diverse alterations in the perinuclear ER subdomain that are suggestive of lipid metabolism perturbations.
