Molecular organization, biochemical function, cellular role and evolution of NfuA, an atypical Fe‐S carrier

Py, Béatrice; Gerez, Catherine; Angelini, Sandra; Planel, Rémy; Vinella, Daniel; Loiseau, Laurent; Talla, Emmanuel; Brochier-Armanet, Céline; Serres, Ricardo Garcia; Latour, Jean‐Marc; Choudens, Sandrine Ollagnier de; Fontecave, Marc; Barras, Frédéric

doi:10.1111/j.1365-2958.2012.08181.x

Cited by 87 publications

(111 citation statements)

References 71 publications

Supporting

Mentioning

102

Contrasting

Unclassified

Order By: Relevance

“…Anti-GroEL teins NfuA (14,15) and a monothiol glutaredoxin, GrxD (16), function as important Fe-S cluster carriers under iron scarcity or oxidative stress conditions, and an iron donor protein, CyaY, modulates the quality of the Fe-S cluster in the presence of excessive amounts of iron (11,12). None of these proteins was identified in our screens, suggesting that these factors are not essential under normal growth conditions.…”

Section: Anti-iscumentioning

confidence: 82%

“…2). The radioactivity levels of ⌬iscU and ⌬iscA mutants (40% and 30%, respectively, of the wildtype 14 C cpm level) were relatively higher than those of the other null mutants (1.3%, 5.1%, 17%, and 27% of the wild-type 14 C cpm level for the ⌬iscS, ⌬hscA, ⌬hscB, and ⌬fdx strains, respectively), consistent with a previous observation that Fe-S enzyme activities are higher in the iscU and iscA mutants than in the iscS, hscA, and fdx strains (31). The results indicate that our new approach is sufficiently sensitive and useful for evaluating the roles of the proteins involved in Fe-S cluster biosynthesis in vivo.…”

Section: Using [2-mentioning

confidence: 99%

“…The second Fe-S cluster assembly system, the sulfur mobilization (SUF) machinery consisting of six proteins encoded by the sufABCDSE operon, operates during stress conditions such as iron starvation, oxidative damage, or heavy metal exposure (8)(9)(10). In addition, several other proteins have potential roles in Fe-S cluster biogenesis: (i) proposed iron donors CyaY (11,12) and ferritin (13); (ii) the putative intermediate Fe-S cluster carrier/scaffold proteins NfuA (14,15), GrxD (16), and Mrp (ApbC) (17); (iii) the IscA/SufA-homologous A-type carrier protein ErpA (18,19); (iv) the putative Fe-S cluster repair protein YtfE (20). Despite extensive studies on Fe-S cluster biosynthesis, defining the molecular mechanism of Fe-S cluster assembly is still a challenge due to the intrinsic chemical nature of Fe-S cluster species.…”

mentioning

confidence: 99%

“…growth (OD 600 ) of the 78 knockout mutants were measured under the same cultivation conditions as the first screen in order to normalize the net radioactivity to cell number, thereby excluding the possibility that the low radioactivity in a mutant is simply due to a growth defect phenotype. For the second screen, a threshold of 50% of the wild-type 14 C cpm · OD 600 Ϫ1 value was employed because the cpm · OD 600 Ϫ1 value of the ⌬iscU strain (14,447) was 48% of that of the wild-type strain (30,123) due to the moderate growth retardation phenotype of the ⌬iscU strain. This additional screen filtered the results down to 65 knockout strains that carried deletions in candidate genes affecting Fe-S cluster biogenesis and iron homeostasis (see Table S2 in the supplemental material).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Global Identification of Genes Affecting Iron-Sulfur Cluster Biogenesis and Iron Homeostasis

et al. 2014

View full text Add to dashboard Cite

bIron-sulfur (Fe-S) clusters are ubiquitous cofactors that are crucial for many physiological processes in all organisms. In Escherichia coli, assembly of Fe-S clusters depends on the activity of the iron-sulfur cluster (ISC) assembly and sulfur mobilization (SUF) apparatus. However, the underlying molecular mechanisms and the mechanisms that control Fe-S cluster biogenesis and iron homeostasis are still poorly defined. In this study, we performed a global screen to identify the factors affecting Fe-S cluster biogenesis and iron homeostasis using the Keio collection, which is a library of 3,815 single-gene E. coli knockout mutants. The approach was based on radiolabeling of the cells with [2-14 C]dihydrouracil, which entirely depends on the activity of an Fe-S enzyme, dihydropyrimidine dehydrogenase. We identified 49 genes affecting Fe-S cluster biogenesis and/or iron homeostasis, including 23 genes important only under microaerobic/anaerobic conditions. This study defines key proteins associated with Fe-S cluster biogenesis and iron homeostasis, which will aid further understanding of the cellular mechanisms that coordinate the processes. In addition, we applied the [2-14 C]dihydrouracil-labeling method to analyze the role of amino acid residues of an Fe-S cluster assembly scaffold (IscU) as a model of the Fe-S cluster assembly apparatus. The analysis showed that Cys37, Cys63, His105, and Cys106 are essential for the function of IscU in vivo, demonstrating the potential of the method to investigate in vivo function of proteins involved in Fe-S cluster assembly.

show abstract

Section: Anti-iscumentioning

confidence: 82%

Section: Using [2-mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Global Identification of Genes Affecting Iron-Sulfur Cluster Biogenesis and Iron Homeostasis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…(Fig. 2) (12,13,(85)(86)(87)(88). Recent in vivo evidence indicates that the mitochondrial protein Nfu1 can interact with the [4Fe-4S] cluster machinery and with potential [4Fe-4S] target proteins, thus supporting its targeting function (89).…”

Section: Synthesis and Trafficking Of The [4fe-4s] Cluster In Mitochomentioning

confidence: 99%

Iron–sulfur cluster biogenesis and trafficking in mitochondria

Braymer

Lill

2017

Journal of Biological Chemistry

314

293

View full text Add to dashboard Cite

The biogenesis of iron-sulfur (Fe/S) proteins in eukaryotes is a multistage, multicompartment process that is essential for a broad range of cellular functions, including genome maintenance, protein translation, energy conversion, and the antiviral response. Genetic and cell biological studies over almost 2 decades have revealed some 30 proteins involved in the synthesis of cellular [2Fe-2S] and [4Fe-4S] clusters and their incorporation into numerous apoproteins. Mechanistic aspects of Fe/S protein biogenesis continue to be elucidated by biochemical and ultrastructural investigations. Here, we review recent developments in the pursuit of constructing a comprehensive model of Fe/S protein assembly in the mitochondrion. Ubiquitous iron-sulfur clusters and their synthesis: an overviewIron-sulfur (Fe/S) 2 clusters are inorganic cofactors that are essential for the proper functioning of virtually all biological cells (1). The chemical versatility of these clusters is utilized in fundamental life processes such as energy production, metabolic conversions, DNA maintenance, gene expression regulation, protein translation, and the antiviral response ( Fig. 1) (2-4). In eukaryotes, Fe/S proteins are found in or associated with the mitochondrion, endoplasmic reticulum, cytosol, and the nucleus. These cofactors participate in electron transfer reactions, Lewis acid catalysis, transfer of sulfur atoms, or facilitating structural roles (5, 6). Although the activities of some Fe/S proteins are dispensable for cell survival under certain conditions, for example fungal Fe/S enzymes in the metabolism of amino acids, others such as Fe/S proteins involved in DNA maintenance or protein translation are essential for cell viability (Fig. 1). The growing number of diseases that implicate Fe/S proteins or their assembly factors illustrates the essentiality of the various functions of these protein cofactors (7-9). The phenotypes associated with these "Fe/S diseases" and the in vivo work in model systems such as Saccharomyces cerevisiae and human cell culture have led to a mechanistic model of eukaryotic Fe/S protein biogenesis, in which the sequence of events required for proper synthesis and trafficking of Fe/S clusters has been elucidated (2). This model has been invaluable to diagnosing new mitochondrial disorders, and its continued advancement will enhance the ability for early diagnosis (10 -13). The focus of this review will be on the latest developments of the functional and mechanistic aspects that have advanced the model of mitochondrial Fe/S protein biogenesis.Cells typically maintain a strict balance of iron and sulfide ion concentrations due to their damaging redox reactions when present in excess (14, 15). The cell also uses a complex biosynthetic system to ensure that the sometimes redox-sensitive and labile Fe/S clusters are assembled correctly, trafficked to specific target apoproteins, and remain protected during these processes. This cellular control is exemplified by the 18 known "Fe/S cluster assembly" (ISC) proteins...

show abstract

Cytosolic iron–sulfur cluster transfer—a proposed kinetic pathway for reconstitution of glutaredoxin 3

2016

View full text Add to dashboard Cite

Iron-sulfur clusters are ubiquitously conserved and play essential cellular roles. The mechanism of Fe-S cluster biogenesis involves multiple proteins in a complex pathway. Cluster biosynthesis primarily occurs in the mitochondria, but key Fe-S proteins also exist in the cytosol. One such protein, glutaredoxin 3 (Grx3), is involved in iron regulation, sensing and mediating [2Fe-2S] cluster delivery to cytosolic protein targets, but the cluster donor for cytosolic Grx3 has not been elucidated. Herein, we delineate the kinetic transfer of [2Fe-2S] clusters into Grx3 from potential cytosolic carrier/scaffold proteins, IscU and Nfu, to evaluate a possible model for Grx3 reconstitution in vivo.

show abstract

Molecular organization, biochemical function, cellular role and evolution of NfuA, an atypical Fe‐S carrier

Abstract: Summary Biosynthesis of iron-sulphur (Fe-S) proteins is cataly-

Cited by 87 publications

References 71 publications

Global Identification of Genes Affecting Iron-Sulfur Cluster Biogenesis and Iron Homeostasis

Global Identification of Genes Affecting Iron-Sulfur Cluster Biogenesis and Iron Homeostasis

Iron–sulfur cluster biogenesis and trafficking in mitochondria

Cytosolic iron–sulfur cluster transfer—a proposed kinetic pathway for reconstitution of glutaredoxin 3

Contact Info

Product

Resources

About