Elucidating the interplay between intracellular Manganese-Iron-ratio and radiotolerance across all domains of life

Abstract Exposure to natural or artificial ionizing radiation induces direct damage to intracellular macromolecules and promotes the formation of reactive oxygen species (ROS), which can further amplify cellular injury. Although many organisms tolerate high radiation doses, the basis of this resilience is not fully understood. A proposed determinant is the intracellular manganese-to-iron ratio (Mn/Fe-ratio), thought to reduce oxidative stress. To evaluate its relevance, Mn and Fe levels were measured in 19 archaeal, bacterial, and two eukaryotic yeast species and compared these values with their survivability after ionizing radiation exposure. There was no consistent relationship between Mn/Fe-ratios and radiation tolerance across this broad phylogenetic range. Integrating our results with prior studies suggests that while elevated Mn/Fe-ratios may contribute to exceptional resistance in certain specialized microorganisms, the ratio is not a reliable, universal predictor of survivability. These findings highlight the multifactorial nature of radiation tolerance and indicate that other processes (e.g. DNA repair mechanisms, antioxidant defenses, and metabolic adaptations) likely play central roles. By clarifying the limitations of Mn/Fe-ratio as a generalizable marker, this study provides a more nuanced understanding of the biochemical determinants of radiation resistance and informs future research into mechanisms of cellular resilience under extreme stress.