[P008] Poster

1:00 PM - 1:50 PM JST(4:00 AM - 4:50 AM UTC)

[P04-472] Role of the HOG pathway in the formaldehyde stress tolerance in the budding yeast

○Yuichiro Ikagawa¹, Saki Sugihara¹, Saki Suzuki¹, Motohiro Tani¹, Masaya Shimada¹, Tomoyuki Nakagawa¹ (1. Gifu University (Japan))

Keywords:

Saccharomyces cerevisiae,stress response,formaldehyde

Formaldehyde (FA) is a highly versatile chemical in industrial applications; however, its high reactivity confers strong cytotoxicity to virtually all living organisms. Despite some reports on cellular FA tolerance mechanisms —including the induction of FA scavenger systems— many aspects remain poorly understood. To elucidate the cellular FA response and the mechanisms by which cells evade FA toxicity, we previously conducted a systematic analysis using the budding yeast Saccharomyces cerevisiae and identified 21 FA resistance-related genes whose deletion confers FA sensitivity. In the present study, we focused on HOG1, a mitogen-activated protein kinase (MAPK) gene among these FA resistance-related genes and investigated the function and role of the Hog1 signaling pathway (HOG pathway) in the FA stress tolerance mechanism.When FA sensitivity was examined in strains carrying deletions of upstream components of the HOG pathway, reduced FA tolerance was observed upon deletion of the Sln1 and Sho1 branches, both of which act upstream of Hog1. In contrast, among strains lacking transcription factors regulated by Hog1p —namely Msn2/4p, Sko1p, Hot1p, and Smp1p— the msn2/4Δ strain exhibited markedly impaired growth under FA stress conditions. These results suggest that the functional expression of Msn2/4p-dependent genes plays a major role in regulating the FA stress tolerance mechanism in the budding yeast. Notably, the sko1Δ strain displayed enhanced FA tolerance compared to the wild-type strain. Transcriptome analysis of S. cerevisiae under FA stress revealed that 2,001 genes were significantly induced more than 2-fold, including genes involved in oxidative stress response, aldehyde metabolism, and DNA damage response. Further investigation into the role of the HOG pathway under FA stress, with a focus on Hog1p as a known FA tolerance factor, demonstrated that both the hog1Δ and msn2/4Δ strains exhibited strong FA sensitivity. Moreover, hog1 deletion partially suppressed the FA-induced upregulation of several genes involved in oxidative stress, aldehyde metabolism, and DNA replication stress responses; however, the induction of most FA-responsive genes was substantially diminished in both deletion strains. Taken together, these findings demonstrate that the HOG pathway plays a critical role in the FA response in the budding yeast, while also revealing the existence of FA tolerance factors regulated independently of the HOG pathway.