|
Title:
|
Saccharomyces cerevisiae glutaredoxin 5-deficient cells subjected to continuous oxidizing conditions are affected in the expression of specific sets of genes
|
|
Author:
|
Bellí i Martínez, Gemma; Molina Navarro, Maria Micaela; García-Martínez, José; Pérez-Ortín, José E.; Herrero Perpiñán, Enrique
|
|
Notes:
|
The Saccharomyces cerevisiae GRX5 gene codes for a
mitochondrial glutaredoxin involved in the synthesis of
iron/sulfur clusters. Its absence prevents respiratory
growth and causes the accumulation of iron inside cells
and constitutive oxidation of proteins. Null ⌬grx5 mu-
tants were used as an example of continuously oxidized
cells, as opposed to situations in which oxidative stress
is instantaneously caused by addition of external oxi-
dants. Whole transcriptome analysis was carried out in
the mutant cells. The set of genes whose expression was
affected by the absence of Grx5 does not significantly
overlap with the set of genes affected in respiratory
petite mutants. Many Aft1-dependent genes involved in
iron utilization that are up-regulated in a frataxin mu-
tant were also up-regulated in the absence of Grx5. BIO5
is another Aft1-dependent gene induced both upon iron
deprivation and in ⌬grx5 cells; this links iron and biotin
metabolism. Other genes are specifically affected under
the oxidative conditions generated by the grx5 muta-
tion. One of these is MLP1, which codes for a homologue
of the Slt2 kinase. Cells lacking MLP1 and GRX5 are
hypersensitive to oxidative stress caused by external
agents and exhibit increased protein oxidation in rela-
tion to single mutants. This in turn points to a role for
Mlp1 in protection against oxidative stress. The genes of
the Hap4 regulon, which are involved in respiratory
metabolism, are down-regulated in ⌬grx5 cells. This ef-
fect is suppressed by HAP4 overexpression. Inhibition of
respiratory metabolism during continuous moderately
oxidative conditions could be a protective response by
the cell. |
|
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:
|
|
