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

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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

par 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 et Vikki M. Weake

Publié: 27 avril 2025
Serveur de preprints: bioRxiv
DOI: 10.1101/2025.04.25.650714

Résumé

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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PREreview Alizée Malnoë et al. du club IU Bloomington Biology

Rédigé par Alizée Malnoë, Mandkhai Molomjamts, Sally Abulaila, Madaline McPherson, Habib Ogunyemi, Warren Wilson, Madison McReynolds, Kimberley Kissoon et 2 autres auteurs du IU Bloomington Biology

The manuscript by Stanhope et al. investigates the role of the one-carbon metabolism enzyme S-Adenosylhomocysteinase (Ahcy) in the alteration of neurodegeneration gene expression in Drosophila. The authors found that oxidation of C195 of Ahcy inhibits its activity, leading to neuroprotective…

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