Maturation of cytosolic iron-sulfur proteins requires glutathione.
Glutathione is the major protective agent against oxidative stress in Saccharomyces cerevisiae. Deletion of the GSH1 gene (strain Deltagsh1) encoding the enzyme that catalyzes the first step of glutathione biosynthesis leads to growth arrest, which can be relieved by either glutathione or reducing agents such as dithiothreitol. Because defects in the biosynthesis of cellular iron-sulfur (Fe/S) proteins are associated with increases in glutathione levels, we examined the consequences of glutathione depletion on this essential process. No significant defects were detected in the amounts, activities, and maturation of mitochondrial Fe/S proteins in glutathione-depleted Deltagsh1 cells. On the contrary, the maturation of extra-mitochondrial Fe/S proteins was decreased substantially. The defect was rectified neither by addition of dithiothreitol nor under anaerobic conditions excluding oxidative damage of Fe/S clusters. A double mutant in GSH1 and ATM1 encoding a mitochondrial ATP binding cassette (ABC) transporter involved in cytosolic Fe/S protein maturation is nonviable even in the presence of dithiothreitol. Similar to atm1 and other mutants defective in cytosolic Fe/S protein maturation, mitochondria from glutathione-depleted Deltagsh1 cells accumulated high amounts of iron. Together, our data demonstrate that glutathione, in addition to its protective role against oxidative damage, performs a novel and specific function in the maturation of cytosolic Fe/S proteins.
Sipos
Katalin
K
Institute of Biochemistry, Medical Faculty, University of Pecs, Szigeti ut 12, 7624 Pecs, Hungary.
Lange
Heike
H
Fekete
Zsuzsanna
Z
Ullmann
Pascaline
P
Lill
Roland
R
Kispal
Gyula
G
D003600:Cytosol / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism* / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
D007506:Iron-Sulfur Proteins; D006861:Hydrogen Peroxide; D005978:Glutathione; D010100:Oxygen