Disease relevance of GRX5

• The disulfide bond in Grx5 could be reduced by GSH but at a rate at least 20 times slower than that observed for the reduction of glutaredoxin 1 from E. coli, a dithiolic glutaredoxin [1].

High impact information on GRX5

• The bulk of mitochondrial iron is normally unavailable to SOD2, but when mitochondrial iron homeostasis is disrupted, for example, by mutations in S. cerevisiae mtm1, ssq1 and grx5, iron accumulates in a reactive form that potently competes with manganese for binding to SOD2, inactivating the enzyme [2].
• In yeast expression assays, AtGRXcp localized to the mitochondria and suppressed the sensitivity of yeast grx5 cells to H2O2 and protein oxidation [3].
• AtGRXcp expression can also suppress iron accumulation and partially rescue the lysine auxotrophy of yeast grx5 cells [3].
• The protein consists of 115 amino acids (12.7 kDa), has a monothiol (CGFS) potential active site and shows high sequence homology to the other monothiol glutaredoxins and especially to yeast Grx5 [4].
• Cells lacking MLP1 and GRX5 are hypersensitive to oxidative stress caused by external agents and exhibit increased protein oxidation in relation to single mutants [5].

Biological context of GRX5

• Grx5 locates at the mitochondrial matrix and is needed for iron/sulfur cluster biogenesis [6].
• 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 [7].

Anatomical context of GRX5

• We found that grx5 was expressed in erythroid cells of zebrafish and mice [8].

Associations of GRX5 with chemical compounds

• Grx5 contains a conserved cysteine residue (Cys-60) and a non-conserved one (Cys-117) [1].
• Gly(115) and Gly(116) could be important for the formation of a glutathione cleft on the Grx5 surface, in contrast to adjacent Cys(117) [9].
• Three-dimensional modeling based on known dithiol glutaredoxin structures predicted a thioredoxin fold structure for Grx5 [9].

Regulatory relationships of GRX5

• Many Aft1-dependent genes involved in iron utilization that are up-regulated in a frataxin mutant were also up-regulated in the absence of Grx5 [5].
• 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 [7].
• Substitution of Phe(50) alters the beta-sheet in the thioredoxin fold structure and inhibits Grx5 function [9].

Other interactions of GRX5

• Null mutation of grx3 did not significantly affect growth and resistance against various oxidants, whereas grx5 mutation caused slow growth and sensitivity toward oxidants such as hydrogen peroxide, paraquat, and diamide [10].
• We have addressed the functional divergence among glutaredoxins by targeting Grx2/3/4 molecules to the mitochondrial matrix using the Grx5 targeting sequence [6].
• The mitochondrial forms of Grx3 and Grx4 partially rescue the defects of a grx5 null mutant [6].
• The Saccharomyces cerevisiae GRX5 gene codes for a mitochondrial glutaredoxin involved in the synthesis of iron/sulfur clusters [5].

References