Expression profile of Yeast Frataxin Mutants
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE44871 | GEO | 2013/03/06
SECONDARY ACCESSION(S): PRJNA192216
REPOSITORIES: GEO
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Project description:Yeast Frataxin Homologue 1 has been involved in oxidative stress and iron-sulfur biogenesis within the mitochondria. We have investigated the expression profile of conditional Yfh1 mutants. Yfh1 depletion leads to activation of iron uptake and repression Two strains were used: WT (strain W303-1A) and tetYFH1 (YFH1 gene under the control of a tet promoter regulatable with doxycycline). We compared the expression profile of tetYFH1 vs tetYFH1 + 10h doxycycline. As control we also compared W303-1A vs W303-1A
2013-03-06 | E-GEOD-44871 | biostudies-arrayexpress
Project description:In mitochondria cysteine desulfurase (Nfs1) plays a central role in the biosynthesis of iron-sulfur (FeS) clusters, cofactors critical for activity of many cellular proteins. Nfs1 functions both as a sulfur donor for cluster assembly and as a binding platform for other proteins functioning in the process. These include, not only the dedicated scaffold protein (Isu1) on which FeS clusters are synthesized, but also frataxin (Yfh1) and ferredoxin (Yah1). Yfh1 activates cysteine desulfurase enzymatic activity, while Yah1 supplies electrons for persulfide reduction. Yfh1 interaction with Nfs1 is well understood; that of Yah1 is not. Here, based on the results of biochemical experiments involving purified wild-type and variant proteins, we report that in Saccharomyces cerevisiae Yah1 and Yfh1 share an evolutionary conserved interaction site on Nfs1. Consistent with this notion each can displace the other from Nfs1, but are inefficient competitors when a variant with an altered interaction site is used. Thus, the binding mode of Yah1 and Yfh1 interacting with Nfs1 in mitochondria of S. cerevisiae resembles the mutually exclusive binding of ferredoxin and frataxin with cysteine desulfurase reported for the bacterial FeS cluster assembly system. Our findings are consistent with the generally accepted scenario that the mitochondrial FeS cluster assembly system was inherited from bacterial ancestors of mitochondria.
2022-04-04 | PXD029519 | Pride
Project description:The biogenesis of iron-sulfur proteins in eukaryotes is an essential process involving the mitochondrial iron-sulfur cluster (ISC) assembly and export machineries and the cytosolic Fe/S protein assembly (CIA) apparatus. To define the integration of Fe/S protein biogenesis into cellular homeostasis, we compared the global transcriptional responses to defects in the three biogenesis systems in S. cerevisiae using DNA microarrays. Microarray analyses were carried out with regulatable yeast mutants in which representatives of each of the three biosynthetic systems could be depleted. In particular, we used the mutants Gal-YAH1, Gal-ATM1 and Gal-NBP35.
2007-12-14 | E-MEXP-1215 | biostudies-arrayexpress
Project description:Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPARγ pathway as a therapeutic target in Friedreich's ataxia Friedreich's ataxia (FRDA), the most common inherited ataxia, is characterized by focal neurodegeneration, diabetes mellitus, and life-threatening cardiomyopathy. Frataxin, which is significantly reduced in patients with this recessive disorder, is a mitochondrial iron-binding protein, but how its deficiency leads to neurodegeneration and metabolic derangements is not known. We performed microarray analysis of heart and skeletal muscle in a mouse model of frataxin deficiency, and found molecular evidence of increased lipogenesis in skeletal muscle, and alteration of fiber-type composition in heart, consistent with insulin resistance and cardiomyopathy, respectively. Since the peroxisome proliferator-activated receptor gamma (PPARγ) pathway is known to regulate both processes, we hypothesized that dysregulation of this pathway could play a key role in frataxin deficiency. We confirmed this by showing a coordinate dysregulation of the PPARγ coactivator Pgc1a and transcription factor Srebp1 in cellular and animal models of frataxin deficiency, and in cells from FRDA patients, who have marked insulin resistance. Finally, we show that genetic modulation of the PPARγ pathway affects frataxin levels in vitro, supporting PPARγ as a novel therapeutic target in FRDA. To compare frataxin deficient (KIKO) mice vs. WT, heart, skeletal muscle, and liver.
2010-04-09 | E-GEOD-15848 | biostudies-arrayexpress
Project description:Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPARγ pathway as a therapeutic target in Friedreich's ataxia Friedreich's ataxia (FRDA), the most common inherited ataxia, is characterized by focal neurodegeneration, diabetes mellitus, and life-threatening cardiomyopathy. Frataxin, which is significantly reduced in patients with this recessive disorder, is a mitochondrial iron-binding protein, but how its deficiency leads to neurodegeneration and metabolic derangements is not known. We performed microarray analysis of heart and skeletal muscle in a mouse model of frataxin deficiency, and found molecular evidence of increased lipogenesis in skeletal muscle, and alteration of fiber-type composition in heart, consistent with insulin resistance and cardiomyopathy, respectively. Since the peroxisome proliferator-activated receptor gamma (PPARγ) pathway is known to regulate both processes, we hypothesized that dysregulation of this pathway could play a key role in frataxin deficiency. We confirmed this by showing a coordinate dysregulation of the PPARγ coactivator Pgc1a and transcription factor Srebp1 in cellular and animal models of frataxin deficiency, and in cells from FRDA patients, who have marked insulin resistance. Finally, we show that genetic modulation of the PPARγ pathway affects frataxin levels in vitro, supporting PPARγ as a novel therapeutic target in FRDA. To compare frataxin deficient (KIKO) mice vs. WT, heart and skeletal muscle. Three replicates (KIKO vs WT), with dye swap
2009-06-02 | E-GEOD-15843 | biostudies-arrayexpress
Project description:Friedreich’s ataxia (FA) is the most common monogenic mitochondrial disease. FA is caused by a depletion of the mitochondrial protein frataxin (FXN), an iron-sulfur (Fe-S) cluster biogenesis factor. To better understand the cellular consequences of FA, we performed genetic interaction mapping in control or FXN edited cells. This screen identified impaired mitochondrial translation downstream of FXN loss, and specifically highlighted the methyltransferase-like protein METTL17 as a candidate effector.
2023-12-18 | GSE242192 | GEO
Project description:Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPARγ pathway as a therapeutic target in Friedreich's ataxia Friedreich's ataxia (FRDA), the most common inherited ataxia, is characterized by focal neurodegeneration, diabetes mellitus, and life-threatening cardiomyopathy. Frataxin, which is significantly reduced in patients with this recessive disorder, is a mitochondrial iron-binding protein, but how its deficiency leads to neurodegeneration and metabolic derangements is not known. We performed microarray analysis of heart and skeletal muscle in a mouse model of frataxin deficiency, and found molecular evidence of increased lipogenesis in skeletal muscle, and alteration of fiber-type composition in heart, consistent with insulin resistance and cardiomyopathy, respectively. Since the peroxisome proliferator-activated receptor gamma (PPARγ) pathway is known to regulate both processes, we hypothesized that dysregulation of this pathway could play a key role in frataxin deficiency. We confirmed this by showing a coordinate dysregulation of the PPARγ coactivator Pgc1a and transcription factor Srebp1 in cellular and animal models of frataxin deficiency, and in cells from FRDA patients, who have marked insulin resistance. Finally, we show that genetic modulation of the PPARγ pathway affects frataxin levels in vitro, supporting PPARγ as a novel therapeutic target in FRDA.
2009-06-02 | GSE15848 | GEO
Project description:Functional genomic analysis of frataxin deficiency reveals tissue-specific alterations and identifies the PPARγ pathway as a therapeutic target in Friedreich's ataxia Friedreich's ataxia (FRDA), the most common inherited ataxia, is characterized by focal neurodegeneration, diabetes mellitus, and life-threatening cardiomyopathy. Frataxin, which is significantly reduced in patients with this recessive disorder, is a mitochondrial iron-binding protein, but how its deficiency leads to neurodegeneration and metabolic derangements is not known. We performed microarray analysis of heart and skeletal muscle in a mouse model of frataxin deficiency, and found molecular evidence of increased lipogenesis in skeletal muscle, and alteration of fiber-type composition in heart, consistent with insulin resistance and cardiomyopathy, respectively. Since the peroxisome proliferator-activated receptor gamma (PPARγ) pathway is known to regulate both processes, we hypothesized that dysregulation of this pathway could play a key role in frataxin deficiency. We confirmed this by showing a coordinate dysregulation of the PPARγ coactivator Pgc1a and transcription factor Srebp1 in cellular and animal models of frataxin deficiency, and in cells from FRDA patients, who have marked insulin resistance. Finally, we show that genetic modulation of the PPARγ pathway affects frataxin levels in vitro, supporting PPARγ as a novel therapeutic target in FRDA.
2009-06-02 | GSE15843 | GEO
Project description:Frataxin (FXN) is involved in mitochondrial iron-sulfur (Fe-S) cluster biogenesis and serves to accelerate Fe-S cluster formation. FXN deficiency is associated with Friedreich ataxia, a neurodegenerative disease. Using chemical cross-linking (XL) accompanied with LC-MS/MS, we studied the the interaction between the core complexes Acp-ISD11-NFS1 (AIN) and AIN-ISCU (AINU) with FXN.
2018-07-11 | PXD006938 | Pride
Project description:Frataxin (FXN) is involved in mitochondrial iron-sulfur (Fe-S) cluster biogenesis and serves to accelerate Fe-S cluster formation. FXN deficiency is associated with Friedreich ataxia, a neurodegenerative disease. Using chemical cross-linking (XL) accompanied with LC-MS/MS, we studied the the interaction between the core complexes Acp-ISD11-NFS1 (AIN) and AIN-ISCU (AINU) with FXN.
2018-07-11 | PXD006928 | Pride