|
Title:
|
Nuclear monothiol glutaredoxins of Saccharomyces cerevisiae can function as mitochondrial glutaredoxins
|
|
Author:
|
Molina Navarro, Maria Micaela; Bellí i Martínez, Gemma; Torre Ruiz, M. A. de la; Rodríguez Manzanaque, Maria Teresa; Herrero Perpiñán, Enrique
|
|
Notes:
|
Glutaredoxins are thiol oxidoreductases that regulate
protein redox state. In Saccharomyces cerevisiae, Grx1
and Grx2 are cytosolic dithiol glutaredoxins, whereas
Grx3, Grx4, and Grx5 are monothiol glutaredoxins. Grx5
locates at the mitochondrial matrix and is needed for
iron/sulfur cluster biogenesis. Its absence causes pheno-
types such as inactivation of iron/sulfur enzymes and
sensitivity to oxidative stress. Whereas Grx5 contains a
single glutaredoxin domain, in Grx3 and Grx4 a thio-
redoxin-like domain is fused to the glutaredoxin do-
main. Here we have shown that Grx3 locates at the nu-
cleus and that the thioredoxin-like domain is required
for such location. We have addressed the functional di-
vergence among glutaredoxins by targeting Grx2/3/4
molecules to the mitochondrial matrix using the Grx5
targeting sequence. The mitochondrial forms of Grx3
and Grx4 partially rescue the defects of a grx5 null mu-
tant. On the contrary, mitochondrially targeted Grx2
does not suppress the mutant phenotype. Both the thi-
oredoxin-like and glutaredoxin domains are needed for
the mitochondrial activity of Grx3, although none of
the cysteine residues at the thioredoxin-like domain is
required for rescue of the grx5 phenotypes. We have
concluded that dithiol glutaredoxins are functionally
divergent from monothiol ones, but the latter can inter-
change their biological activities when compartment
barriers are surpassed. |
|
Rights:
|
(c) The American Society for Biochemistry and Molecular Biology, 2004
|
|
Document type:
|
article
publishedVersion |
|
Published by:
|
The American Society for Biochemistry and Molecular Biology
|
|
Share:
|
|
