Moh1 coordinates ROS-dependent apoptosis in genotoxic stress response of Candida albicans.

Candida albicans employs apoptosis to maintain genomic stability under genotoxic stress, yet its regulatory mechanisms remain poorly defined. Here, we characterize the role of a putative pro-apoptotic factor Moh1 in C. albicans. Our findings reveal that MOH1 transcription is significantly upregulated under genotoxic stress and in DNA repair-deficient backgrounds (e.g., rad52Δ). Paradoxically, MOH1 deletion enhances resistance to genotoxic agents, improving cellular survival and reducing apoptosis, as evidenced by decreased nuclear condensation. Mechanistically, moh1Δ cells exhibit reduced intracellular reactive oxygen species (ROS), and pharmacological ROS scavenging with N-acetylcysteine abolishes the stress-resistant phenotype. Genetic interaction analysis identifies potential functional overlap between MOH1 and NMA111, a previously characterized pro-apoptotic factor. Transcriptomic profiling of moh1Δ cells under genotoxic stress shows dysregulation of DNA repair (SPO11, RFC52) and apoptosis (Orf19.2175) genes. While dispensable for hyphal morphogenesis and virulence in a Galleria mellonella model, Moh1 negatively regulates biofilm formation. Collectively, these findings establish Moh1 as a critical regulator of ROS-dependent apoptosis during genotoxic stress response in C. albicans, offering insights for targeting fungal apoptotic pathways in antifungal strategies.