Molecular Mechanisms of Formaldehyde Toxicity and Tolerance in Budding Yeast Saccharomyces cerevisiae

Abstract

Formaldehyde is a highly reactive one‑carbon aldehyde that induces cytotoxicity through DNA–protein crosslinks, RNA adduct formation, and disruption of cellular redox homeostasis. Because all living cells must counteract these lesions to survive, elucidating formaldehyde detoxification and tolerance mechanisms is essential for understanding formaldehyde stress biology. The budding yeast Saccharomyces cerevisiae provides a genetically tractable model for dissecting formaldehyde‑induced molecular damage and the pathways that mitigate it. This review summarizes key mechanisms of formaldehyde tolerance in budding yeast, including glutathione‑dependent formaldehyde detoxification, aldehyde and alcohol metabolic networks, DNA and RNA repair pathways, and other protective mechanisms. As many of these mechanisms are evolutionarily conserved, insights gained from budding yeast offer a valuable framework for understanding formaldehyde toxicity across eukaryotes and may contribute to the development of strategies to mitigate formaldehyde‑related cellular damage.