Expression of the human ferritin light chain in a frataxin mutant yeast affects ageing and cell death.
Ferritin is one of the major eukaryotic proteins involved in regulating iron metabolism and maintaining iron homeostasis. However, Saccaromyces cerevisiae is an exception, possessing no ferritin and using other means to store excess iron. The only potential iron storage protein identified in yeast so far is the homologue of human frataxin (YFH1p). In this study, we found that dysfunction of yeast frataxin shortens mean lifespan by 49% compared to the WT control. Interestingly, the human ferritin L gene can, at least partially, complement the function of yeast frataxin, extending lifespan and protecting cells from death induced by oxidative stress or excess iron. Our findings indicate that ferritin L can perform functions in yeast that are similar to its functions in mammals, and suggest that common mechanisms may exist for preventing iron and oxidative damage in single- and multi-cellular eukaryotic organisms. Clearly, elucidation of the function of human ferritin in yeast would help in gaining a better understanding the molecular basis of iron storage diseases.
Desmyter
Liesbeth
L
Fundamental and Applied Molecular Biology, Ghent University and Flanders Interuniversity Institute for Biotechnology, VIB Technologiepark 927 B-9052, Ghent Zwijnaarde, Belgium.
Dewaele
Sylviane
S
Reekmans
Rieka
R
Nystrom
Thomas
T
Contreras
Roland
R
Chen
Cuiying
C
D000375:Aging / Q000235:genetics* / Q000502:physiology; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D005293:Ferritins / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development; D000096923:Frataxin
D005293:Ferritins; D005656:Fungal Proteins; D033862:Iron-Binding Proteins; D000096923:Frataxin