One-carbon metabolism influences gene expression by providing methyl units for DNA, RNA, and histone methylation. Robust methylation requires rapid hydrolysis of the methylation by-productS-adenosylhomocysteine (SAH) byS-adenosylhomocysteinase (Ahcy). Here, we show Ahcy is a redox-sensitive enzyme that is inhibited by oxidation of a conserved cysteine, C195,in vitroandin vivo. Transient oxidation of Ahcy is neuroprotective in aDrosophilalight stress model where it results in rapid gene expression changes and protects against retinal degeneration. Thus, redox sensing by the one-carbon metabolic enzyme Ahcy enables rapid changes in gene expression in response to changes in redox homeostasis.
