How plant metabolic flux alters gene expression to optimize plant growth and response to stress remains largely unclear.Here,we report that Arabidopsis thaliana NAD+-dependent histone deacetylase AtSRT1 negatively regulates plant tolerance to stress and glycolysis but stimulates mitochondrial respiration.We found that AtSRT1 interacts with Arabidopsis cMyc-Binding Protein 1 (AtMBP-1),a transcriptional repressor produced by alteative translation of the cytosolic glycolytic enolase gene LOS2/ENO2.We demonstrated that AtSRT1 could associate with the chromatin of AtMBP-1 targets LOS2/ENO2 and STZ/ZAT10,both of which encode key stress regulators,and reduce the H3K9ac levels at these genes to repress their transcription.Overexpression of both AtSRT1 and AtMBP-1 had synergistic effects on the expression of glycolytic genes,glycolytic enzymatic activities,and mitochondrial respiration.Furthermore,we found that AtMBP-1 is lysine-acetylated and vulnerable to proteasomal protein degradation,while AtSRT1 could remove its lysine acetylation and significantly enhance its stability in vivo.Taken together,these results indicate that AtSRT1 regulates primary metabolism and stress response by both epigenetic regulation and modulation of AtMBP-1 transcriptional activity in Arabidopsis.