An Expansion of the Endoplasmic Reticulum that Halts Autophagy is Permissive to Genome Instability

Author:

Lara-Barba Eliana1,Torán-Vilarrubias Alba1,Moriel-Carretero María2ORCID

Affiliation:

1. Institut de Génétique Humaine (IGH), Université de Montpellier-Centre National de la Recherche Scientifique, Montpellier, France

2. Centre de Recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier-Centre National de la Recherche Scientifique, Montpellier, France

Abstract

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.

Funder

ATIP-Avenir

Agence Nationale de la Recherche

Fondation L’Oréal-UNESCO

Institut National Du Cancer

Publisher

SAGE Publications

Subject

General Materials Science

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