We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The histone methyltransferase G9a regulates tolerance to oxidative stress–induced energy consumption.
- Authors
Riahi, Human; Brekelmans, Carlijn; Foriel, Sarah; Merkling, Sarah H.; Lyons, Taylor A.; Itskov, Pavel M.; Kleefstra, Tjitske; Ribeiro, Carlos; van Rij, Ronald P.; Kramer, Jamie M.; Schenck, Annette
- Abstract
Stress responses are crucial processes that require activation of genetic programs that protect from the stressor. Stress responses are also energy consuming and can thus be deleterious to the organism. The mechanisms coordinating energy consumption during stress response in multicellular organisms are not well understood. Here, we show that loss of the epigenetic regulator G9a in Drosophila causes a shift in the transcriptional and metabolic responses to oxidative stress (OS) that leads to decreased survival time upon feeding the xenobiotic paraquat. During OS exposure, G9a mutants show overactivation of stress response genes, rapid depletion of glycogen, and inability to access lipid energy stores. The OS survival deficiency of G9a mutants can be rescued by a high-sugar diet. Control flies also show improved OS survival when fed a high-sugar diet, suggesting that energy availability is generally a limiting factor for OS tolerance. Directly limiting access to glycogen stores by knocking down glycogen phosphorylase recapitulates the OS-induced survival defects of G9a mutants. We propose that G9a mutants are sensitive to stress because they experience a net reduction in available energy due to (1) rapid glycogen use, (2) an inability to access lipid energy stores, and (3) an overinduced transcriptional response to stress that further exacerbates energy demands. This suggests that G9a acts as a critical regulatory hub between the transcriptional and metabolic responses to OS. Our findings, together with recent studies that established a role for G9a in hypoxia resistance in cancer cell lines, suggest that G9a is of wide importance in controlling the cellular and organismal response to multiple types of stress.
- Subjects
ENERGY consumption; GENETICS; DROSOPHILA; GLYCOGEN phosphorylase; HYPOXEMIA
- Publication
PLoS Biology, 2019, Vol 17, Issue 3, p1
- ISSN
1544-9173
- Publication type
Article
- DOI
10.1371/journal.pbio.2006146