Grx5 is a mitochondrial glutaredoxin required for the activity of iron/sulfur enzymes.
Yeast cells contain a family of three monothiol glutaredoxins: Grx3, 4, and 5. Absence of Grx5 leads to constitutive oxidative damage, exacerbating that caused by external oxidants. Phenotypic defects associated with the absence of Grx5 are suppressed by overexpression of SSQ1 and ISA2, two genes involved in the synthesis and assembly of iron/sulfur clusters into proteins. Grx5 localizes at the mitochondrial matrix, like other proteins involved in the synthesis of these clusters, and the mature form lacks the first 29 amino acids of the translation product. Absence of Grx5 causes: 1) iron accumulation in the cell, which in turn could promote oxidative damage, and 2) inactivation of enzymes requiring iron/sulfur clusters for their activity. Reduction of iron levels in grx5 null mutants does not restore the activity of iron/sulfur enzymes, and cell growth defects are not suppressed in anaerobiosis or in the presence of disulfide reductants. Hence, Grx5 forms part of the mitochondrial machinery involved in the synthesis and assembly of iron/sulfur centers.
Rodríguez-Manzaneque
María Teresa
MT
Departament de Ciències Mèdiques Bàsiques, Facultat de Medicina, Universitat de Lleida, 25198-Lleida, Spain.
Tamarit
Jordi
J
Bellí
Gemma
G
Ros
Joaquim
J
Herrero
Enrique
E
D000595:Amino Acid Sequence; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D015153:Blotting, Western; D018076:DNA, Complementary / Q000378:metabolism; D054477:Glutaredoxins; D007501:Iron / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010084:Oxidation-Reduction; D010088:Oxidoreductases; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism* / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013997:Time Factors; D024483:Vitamin K 3 / Q000494:pharmacology
D000933:Antifibrinolytic Agents; D018076:DNA, Complementary; D054477:Glutaredoxins; D007506:Iron-Sulfur Proteins; D010455:Peptides; D011506:Proteins; D024483:Vitamin K 3; D007501:Iron; D010088:Oxidoreductases; D010100:Oxygen