Combining data from genomes, Y2H and 3D structure indicates that BolA is a reductase interacting with a glutaredoxin

Huynen, Martijn; Spronk, Chris A. E. M.; Gabaldón, Toni; Snel, Berend

doi:10.1016/j.febslet.2004.11.111

Cited by 78 publications

(91 citation statements)

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“…In bacterial operons, BolA tends to occur not only with a monothiol glutaredoxin, but also with proteins involved in defense against oxidative stress: glutathione-S-transferase and Toluene exporters (16). We found, however, no evidence for upregulation of BOLA1 under conditions of oxidative stress in human gene expression data (Supplementary Table S2).…”

Section: Willems Et Alcontrasting

confidence: 43%

“…Here we provide first evidence that BOLA1 might exert such a role and that one of the target proteins of the BOLA1/GLRX5 complex is involved in maintaining the normal mitochondrial shape. It should thereby be noted that, although BolA's 3D structure is similar to that of the bacterial reductase OsmC, suggesting a reducing activity of BolA itself, BolA1 does not contain any conserved cysteines, rendering any reducing function dependent on an external source of reducing equivalents (16).…”

Section: Discussionmentioning

confidence: 99%

“…The BolA-like protein family displays a phylogenetic distribution that is very similar to that of the monothiol glutaredoxins (9,16), and yeast BolA2 was indeed demonstrated to interact with cytosolic monothiol glutaredoxins Grx3 and Grx4 (23). As human mitochondria contain the monothiol glutaredoxin GLRX5 (30) (Fig.…”

Section: Bola1 Is Complexed With Glrx5mentioning

confidence: 99%

“…BolA in E. coli is involved in the regulation of cell wall proteins PBP5, PBP6, and AmpC (32), but its exact molecular function remains unknown. Comparative genomics analyses have pointed to an interaction of BolA with monothiol glutaredoxins, based on gene order conservation (16), phylogenetic distribution (16), and a physical interaction between BolA homolog 2 and Grx3/4 in Saccharomyces cerevisiae (14,17) and Drosophila melanogaster (11).…”

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confidence: 99%

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BOLA1 Is an Aerobic Protein That Prevents Mitochondrial Morphology Changes Induced by Glutathione Depletion

Willems

Wanschers

Esseling

et al. 2013

Antioxidants & Redox Signaling

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Aims: The BolA protein family is widespread among eukaryotes and bacteria. In Escherichia coli, BolA causes a spherical cell shape and is overexpressed during oxidative stress. Here we aim to elucidate the possible role of its human homolog BOLA1 in mitochondrial morphology and thiol redox potential regulation. Results: We show that BOLA1 is a mitochondrial protein that counterbalances the effect of L-buthionine-(S,R)-sulfoximine (BSO)-induced glutathione (GSH) depletion on the mitochondrial thiol redox potential. Furthermore, overexpression of BOLA1 nullifies the effect of BSO and S-nitrosocysteine on mitochondrial morphology. Conversely, knockdown of the BOLA1 gene increases the oxidation of mitochondrial thiol groups. Supporting a role of BOLA1 in controlling the mitochondrial thiol redox potential is that BOLA1 orthologs only occur in aerobic eukaryotes. A measured interaction of BOLA1 with the mitochondrial monothiol glutaredoxin GLRX5 provides hints for potential mechanisms behind BOLA1's effect on mitochondrial redox potential. Nevertheless, we have no direct evidence for a role of GLRX5 in BOLA1's function. Innovation: We implicate a new protein, BOLA1, in the regulation of the mitochondrial thiol redox potential. Conclusion: BOLA1 is an aerobic, mitochondrial protein that prevents mitochondrial morphology aberrations induced by GSH depletion and reduces the associated oxidative shift of the mitochondrial thiol redox potential. Antioxid. Redox Signal. 18, 129-138.

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Section: Willems Et Alcontrasting

confidence: 43%

Section: Discussionmentioning

confidence: 99%

Section: Bola1 Is Complexed With Glrx5mentioning

confidence: 99%

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confidence: 99%

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BOLA1 Is an Aerobic Protein That Prevents Mitochondrial Morphology Changes Induced by Glutathione Depletion

Willems

Wanschers

Esseling

et al. 2013

Antioxidants & Redox Signaling

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“…Fra2 is a member of a protein family of unknown function, which is named after one of the E. coli members, BolA. BolAlike proteins have been hypothesized to work together with monothiol glutaredoxins based on computational and biochemical analyses (28). Recently, a chloroplast-localized protein homologous to BolA was identified that participates in chloroplast Fe-S synthesis of Arabidopsis thaliana (29).…”

Section: Discussionmentioning

confidence: 99%

Identification of FRA1 and FRA2 as Genes Involved in Regulating the Yeast Iron Regulon in Response to Decreased Mitochondrial Iron-Sulfur Cluster Synthesis

Kumánovics

Chen

et al. 2008

Journal of Biological Chemistry

203

262

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The nature of the connection between mitochondrial Fe-S cluster synthesis and the iron-sensitive transcription factor Aft1 in regulating the expression of the iron transport system in Saccharomyces cerevisiae is not known. Using a genetic screen, we identified two novel cytosolic proteins, Fra1 and Fra2, that are part of a complex that interprets the signal derived from mitochondrial Fe-S synthesis. We found that mutations in FRA1 (YLL029W) and FRA2 (YGL220W) led to an increase in transcription of the iron regulon. In cells incubated in high iron medium, deletion of either FRA gene results in the translocation of the low iron-sensing transcription factor Aft1 into the nucleus, where it occupies the FET3 promoter. Deletion of either FRA gene has the same effect on transcription as deletion of both genes and is not additive with activation of the iron regulon due to loss of mitochondrial Fe-S cluster synthesis. These observations suggest that the FRA proteins are in the same signal transduction pathway as Fe-S cluster synthesis. We show that Fra1 and Fra2 interact in the cytosol in an iron-independent fashion. The Fra1-Fra2 complex binds to Grx3 and Grx4, two cytosolic monothiol glutaredoxins, in an iron-independent fashion. These results show that the Fra-Grx complex is an intermediate between the production of mitochondrial Fe-S clusters and transcription of the iron regulon.Iron is an essential element required for all eukaryotes and most prokaryotes. Iron is also potentially dangerous, since it can participate in the generation of toxic oxygen molecules, such as superoxide anion and the hydroxyl radical. Iron transport is highly regulated in all species, and iron transporters are only expressed under conditions of iron need. Transcriptional and post-transcriptional regulation of iron transport systems occurs in all organisms ranging from yeast to humans. Consequently, iron acquisition in all species is tightly controlled and is coordinated with iron use. The budding yeast Saccharomyces cerevisiae expresses two different high affinity iron transport systems. One system is composed of a closely related family of four siderophore transporters. Siderophores are small organic molecules that exhibit an extremely high affinity (K d ϭ 10 Ϫ33 ) for iron (1). Although S. cerevisiae does not synthesize siderophores, it can accumulate siderophores produced by other organisms. The second high affinity iron transport system mediates the acquisition of ionic iron and is composed of a cell surface multicopper oxidase, Fet3, and a transmembrane permease, Ftr1. The multicopper oxidase converts Fe 2ϩ to Fe 3ϩ , which is then transported by the transmembrane permease.The transcriptional activator Aft1 regulates both high affinity iron transport systems (2). Aft1 is cytosolic when cells are iron-replete, but under conditions of iron depletion, Aft1 translocates into the nucleus, where it activates the transcription of ϳ20 genes (3). These genes, referred to as the iron regulon, include the siderophore transporters, the high affini...

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FeSCluster Assembly:SUFSystem in Bacteria, Plastids and Archaea

Dong

Witcher

Outten

et al. 2017

Encyclopedia of Inorganic and Bioinorganic Chemistry

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Iron–sulfur (Fe–S) clusters are essential cofactors in biology due to their use in critical pathways such as nitrogen fixation, photosynthesis, and respiration. Fe–S cluster biogenesis requires complex systems to mobilize iron and sulfide, assemble the nascent cluster, and target Fe–S clusters to downstream target proteins. All of these steps must be coordinated to protect Fe–S cluster biogenesis intermediates from reactive oxygen species and other stressors. Multiple Fe–S cluster biogenesis pathways exist in different organisms and organelles. The Suf ( su lfur f ormation) pathway is phylogenetically the most ancient of the cluster biogenesis systems and is distributed across all domains of life. It can be found as the primary Fe–S cluster biogenesis pathway or as an auxiliary pathway adapted to maintain Fe–S cluster metabolism under stress conditions. Here we describe the biochemical, genetic, and physiological characterization of the Suf system, in all of its iterations.

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Combining data from genomes, Y2H and 3D structure indicates that BolA is a reductase interacting with a glutaredoxin

Cited by 78 publications

References 39 publications

BOLA1 Is an Aerobic Protein That Prevents Mitochondrial Morphology Changes Induced by Glutathione Depletion

BOLA1 Is an Aerobic Protein That Prevents Mitochondrial Morphology Changes Induced by Glutathione Depletion

Identification of FRA1 and FRA2 as Genes Involved in Regulating the Yeast Iron Regulon in Response to Decreased Mitochondrial Iron-Sulfur Cluster Synthesis

FeSCluster Assembly:SUFSystem in Bacteria, Plastids and Archaea

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