Increased iron supplied through Fet3p results in replicative life span extension of Saccharomyces cerevisiae under conditions requiring respiratory metabolism

We have previously shown that copper supplementation extends the replicative life span of Saccharomyces cerevisiae when grown under conditions forcing cells to respire. We now show that copper's effect on life span is through Fet3p, a copper containing enzyme responsible for high affinity transport of iron into yeast cells. Life span extensions can also be obtained by supplementing the growth medium with 1 mM ferric chloride. Extension by high iron levels is still dependent on the presence of Fet3p. Life span extension by iron or copper requires growth on media containing glycerol as the sole carbon source, which forces yeast to respire. Yeast grown on glucose containing media supplemented with iron show no extension of life span. The iron associated with cells grown in media supplemented with copper or iron is 1.4–1.8 times that of cells grown without copper or iron supplementation. As with copper supplementation, iron supplementation partially rescues the life span of superoxide dismutase mutants. Cells grown with copper supplementation display decreased production of superoxide as measured by dihydroethidium staining.

► Increased yeast life span by copper is dependent on the ferroxidase Fet3p.
► Iron supplementation also results in a Fet3p dependent increase in life span.
► Respiration is necessary for the increase in life span by iron supplementation.
► Cells grown with copper or iron supplementation contain more iron.
► Iron supplementation partially rescues the life span of SOD mutants.