Prokaryotic and eukaryotic monothiol glutaredoxins are able to perform the functions of Grx5 in the biogenesis of Fe/S clusters in yeast mitochondria

Abstract

The Saccharomyces cerevisiae monothiol glutaredoxin Grx5 participates in the mitochondrial biogenesis of iron-sulfur clusters. Grx5 homologues exist in organisms from bacteria to humans. Chicken (cGRX5) and human (hGRX5) homologues contain a mitochondrial targeting sequence, suggesting a mitochondrial localization for these two proteins. We have compartmentalized the Escherichia coli and Synechocystis sp. homologues, and also cGRX5 and hGRX5, in the mitochondrial matrix of a yeast grx5 mutant. All four heterologous proteins rescue the defects of the mutant. The chicken cGRX5 gene was significantly expressed throughout the embryo stages in different tissues. These results underline the functional conservation of Grx5 homologues throughout evolution.

Structural insights into the N-terminal GIY–YIG endonuclease activity of Arabidopsis glutaredoxin AtGRXS16 in chloroplasts

“…S5). This result was unexpected given the functional interchangeability among CGFS type Grxs (8,17,18). Interestingly, the poplar chloroplastic PtGRXS16 appears to target to yeast mitochondria and is functional in yeast suppression assays (25).…”

“…Previous reports suggest that CGFS-type monothiol Grxs bind an iron-sulfur cluster (20,21) and suppress yeast grx5 mutant phenotypes (8). AtGRXS16 purified from Escherichia coli cells displayed a dark-brown color, but the color faded quickly.…”

“…Recent advances in the biochemical analysis of CGFS-type Grxs suggest conserved structural features and the interchangeability of their functions (7). CGFS-type Grxs from plants and metazoan are able to perform the functions of Saccharomyces cerevisiae Grx5 (ScGrx5) in the biogenesis of Fe-S clusters in yeast mitochondria (8). However, Plasmodium falciparum glutaredoxinlike protein 1 (PfGLP1) does not bind a Fe-S cluster (9) and in Pteris vittata Grx5 (PvGrx5), the Cys 67 residue at the N-terminal region, not the Cys 108 at the "CGFS" motif, is required for Grx activity and arsenic resistance (10).…”

Mono- and Dithiol Glutaredoxins in the Trypanothione-Based Redox Metabolism of Pathogenic Trypanosomes

“…3) (11,73,87,88). Complementation studies using a yeast mutant defective in mitochondrial Grx5, which is unable to maturate iron-sulfur proteins and accumulates toxic levels of intracellular iron, demonstrated the evolutionary conserved function for 1-CGrxs from different eukaryotic and prokaryotic organisms (11,13,61,87). Intriguingly, respective experiments with the three T. brucei 1-C-Grxs revealed that only 1-C-Grx1 modestly rescued the mutant phenotype (27).…”

“…Instead, the capability to coordinate ISCs appears to be a common feature for 1-C-Grxs (16,40,42,43,54,67,89) with yeast Grx7 being, so far, the only known exception (59,60). The latter feature determines an evolutionary conserved and indispensable role of 1-C-Grxs in the biogenesis and assembly of iron-sulfur proteins (11,61) and other cell-specific regulatory functions such as the (in)activation of nuclear transcription factors (35,62,86).…”