Epigenetic regulator G9a provides glucose as a sweet key to stress resistance.

The ability to adapt to acute and chronic stress is important for organisms to thrive in evolutionary niches and for cells to survive in adverse conditions. The regulatory networks that control stress responses are evolutionarily conserved, and many factors that selectively activate stress responses have been identified. Less well understood are mechanisms that guard against unnecessary induction of cytoprotective factors and that connect stress responses with cellular metabolism to control energy expenditure during stress. The work of Riahi and colleagues represents important progress in this regard because it identifies the histone methyltransferase G9a as a modulator of oxidative stress responses. G9a dampens the expression of antioxidant genes, thus preventing inappropriate energy consumption. Moreover, G9a promotes the well-paced catabolism of storage glycogen and fat during stress. The importance of energy availability during stress is further evidenced by exogenous glucose rescuing the vulnerability of the G9a mutant to oxidative stress. Prior work in multiple model systems has implicated G9a in several other adaptive responses. Therefore, its role in pacing energy consumption and in restraining excessive stress response gene expression under stress may extend to other adaptive responses across species.