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

Eliana Lara-Barba, Alba Torán-Vilarrubias, María Moriel-Carretero*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
JournalContact
Volume6
DOIs
StatePublished - 1 Jan 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author(s) 2023.

Keywords

  • DNA DSBs
  • Silybum marianum
  • autophagy
  • endoplasmic reticulum
  • genome instability
  • homologous recombination

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