Expression of the human ferritin light chain in a frataxin mutant yeast affects ageing and cell death

• Published in: Experimental gerontology Vol. 39; no. 5; pp. 707 - 715
• Main Authors: Desmyter, Liesbeth, Dewaele, Sylviane, Reekmans, Rieka, Nystrom, Thomas, Contreras, Roland, Chen, Cuiying
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.05.2004
• Subjects: Ageing; Aging - genetics; Aging - physiology; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Cell Death - genetics; Cell Death - physiology; Ferritin L; Ferritins - genetics; Frataxin; Fungal Proteins - genetics; Fungal Proteins - physiology; Gene Expression - genetics; Humans; Iron stress; Iron-Binding Proteins - genetics; Lifespan; Mutation - genetics; Oxidative stress; Oxidative Stress - genetics; Oxidative Stress - physiology; Saccaromyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Oxidative stress; Frataxin; Ageing; Iron stress; Ferritin L; Lifespan; Saccaromyces cerevisiae
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2004.01.008

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.