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One-carbon metabolism enzyme Ahcy is a redox sensor that modulates gene expression to protect against light stress-induced retinal degeneration

de Sarah C. Stanhope, Kratika Singhal, Nicolás M. Morato, Yunfei Feng, Gaoya Meng, Makayla N. Marlin, Claudia C. Kotanko, Madolyn M. Jarrett, Andrew D. Mesecar, Graham R. Cooks e Vikki M. Weake

Publicado: 27 de abril de 2025
Servidor: bioRxiv
DOI: 10.1101/2025.04.25.650714

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). Here, we show Ahcy is a redox-sensitive enzyme that is inhibited by oxidation of a conserved cysteine, C195, in vitro and in vivo . Transient oxidation of Ahcy is neuroprotective in a Drosophila light 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.

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