<i>Drosophila</i> Ahcy is a redox sensor that modulates gene expression to protect against light stress-induced retinal degeneration.

ABSTRACT: 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-product S-adenosylhomocysteine (SAH) by S-adenosylhomocysteinase (Ahcy). Ahcy is essential for maintaining methylation potential; however, the mechanisms governing its enzymatic activity, particularly in response to cellular stress, remain largely uncharacterized. Here, we show Ahcy is a redox-sensitive enzyme that is inhibited by oxidation of a conserved cysteine, C195, in vitro resulting in elevated SAH levels upon oxidative stress in vivo. We leveraged High-Throughput Desorption Electrospray Ionization Mass Spectrometry to directly quantify Ahcy enzymatic activity and observed that H₂

SUBMITTER: Stanhope SC 

PROVIDER: S-EPMC12478188 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature