Heterologous Expression of Either Human or Soya Bean Ferritins in Budding Yeast Reveals Common Functions Protecting Against Oxidative Agents and Counteracting Double-Strand Break Accumulation.

Abstract

Ferritins are globular proteins that, upon self-assembly in nanocages, are capable of bio-safely storing huge concentrations of bioavailable iron. They are present in most cell types and organisms; one of the exceptions is yeast. Heterologous expression of either human or vegetal ferritins in Saccharomyces cerevisiae revealed new and unknown functions for soya bean ferritins; validated this model by confirming previously characterized functions in human ferritins and also demonstrated that, like human H chain, vegetal H1, and H2 chains also shown a tendency to localize in the nucleus when expressed in an eukaryotic cell model lacking plastids and chloroplasts. Furthermore, when expressed in the system budding yeast, the four ferritins (human H and L and soya bean H1 and H2 chains) present equivalent and relevant functions as protectors against oxidative damage and against the accumulation of double-strand breaks in the DNA. We present evidence demonstrating that these effects are exclusively observed with oxidative agents that operate through the Fenton reaction, such as H₂O₂. Here, we also discuss the ferritin requirement for N-glycosylation to exert these functions. We believe that our approach might contribute to extending the knowledge around ferritin function and its consequent relevance to human health.