Cell death in Ustilago maydis: comparison with other fungi and the effect of metformin and curcumin on its chronological lifespan.

ABSTRACT

Ustilago maydis is a Basidiomycota fungus, in which very little is known about its mechanisms of cell survival and death. To date, only the role of metacaspase1, acetate and hydrogen peroxide as inducers of cell death has been investigated. In the present work, we analyzed the lifespan of U. maydis compared with other species like Sporisorium reilianum, Saccharomyces cerevisiae and Yarrowia lipolytica, and we observed that U. maydis has a minor lifespan. We probe the addition of low concentrations metformin and curcumin to the culture media, and we observed that both prolonged the lifespan of U. maydis, a result observed for the first time in a phytopathogen fungus. However, higher concentrations of curcumin were toxic for the cells, and interestingly induced the yeast-to-mycelium dimorphic transition. The positive effect of metformin and curcumin appears to be related to an inhibition of the mechanistic Target of Rapamycin (mTOR) pathway, increase expression of autophagy genes and reducing of reactive oxygen species. These data indicate that U. maydis may be a eukaryotic model organism to elucidate the molecular mechanism underlying apoptotic and necrosis pathways, and the lifespan increase caused by metformin and curcumin.