Yippee-like protein Moh1 links gene expression to metabolism and selective stress resistance in Saccharomyces cerevisiae.

Abstract

The Yippee-like (YPEL) proteins are a evolutionarily conserved eukaryotic family implicated in proliferation, senescence, and stress adaptation, yet their molecular functions remain poorly defined. Humans possess five paralogs (YPEL1-YPEL5), while the budding yeast S. cerevisiae contains a single ortholog, MOH1, previously linked to stress responses but with an unclear cellular role. Here, we investigated the function of MOH1 in S. cerevisiae. MOH1 deletion resulted in stress-specific phenotypes, including increased sensitivity to sodium azide and sulfuric acid, but enhanced resistance to hydrogen peroxide and acetic acid. Moh1 protein levels were dynamically regulated, decreasing upon hydrogen peroxide treatment and increasing in response to sulfuric acid. Morphological analyses including SEM revealed that moh1 $\Delta$ cells are rounder, form aggregates, and exhibit altered surface architecture independently of stress. RNA profiling and FTIR spectroscopy uncovered transcriptional reprogramming and metabolic remodeling, including alterations in lipid, protein, and cell wall polysaccharide levels and composition. Functional analyses showed that increased resistance to hydrogen peroxide is not due to altered mitochondrial ROS production but rather to reduced intracellular ROS accumulation. This effect is attributed to decreased cellular uptake resulting from altered permeability, supported by resistance to Congo red and sensitivity to SDS, consistent with cell envelope remodeling. Collectively, our findings identify Moh1 as a regulatory factor linking gene expression to metabolism and cellular architecture, thereby influencing cell envelope permeability and conferring selective stress resistance in S. cerevisiae.