Structural and Spectroscopic Insights into BolA-Glutaredoxin Complexes

Roret, Thomas; Tsan, Pascale; Couturier, Jérémy; Zhang, Bo; Johnson, Michael K.; Rouhier, Nicolas; Didierjean, Claude

doi:10.1074/jbc.m114.572701

Cited by 45 publications

(91 citation statements)

References 60 publications

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“…A physiological relevance of a Grx-Bol heterodimer has been established only for the yeast cytosolic monothiol glutaredoxin Grx3 and Bol2 (formerly known as Fra2), which are involved in iron homeostasis in the yeast cytosol (94 -96). Similar Fe/S cluster-containing Bol-Grx heterocomplexes have been observed in bacteria (BolA with GrxD or Grx4), plants (BolA1 and BolA2 with GrxS14 and GrxS17), and recently in humans (BOLA1 and BOLA3 with GLRX5) (93,97,98). Mitochondrial Bol1 proteins contain three conserved histidine residues, and Bol3 contains a histidine and a cysteine residue as candidates for coordination of the [2Fe-2S] cluster in the heterodimers with Grx5 (Fig.…”

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

confidence: 59%

Iron–sulfur cluster biogenesis and trafficking in mitochondria

Braymer

Lill

2017

Journal of Biological Chemistry

314

293

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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...

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

confidence: 59%

Iron–sulfur cluster biogenesis and trafficking in mitochondria

Braymer

Lill

2017

Journal of Biological Chemistry

314

293

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“…A similar defect in Fe bioavailability was observed in zebrafish (Danio rerio) and HeLa cells when HsGRX3 (or the zebrafish ortholog) was depleted (Mühlenhoff et al, 2010;Haunhorst et al, 2013). In plants, BolA2 does not seem to play a role in Fe homeostasis, and the biological output of the GRXS17-BolA2 interaction remains an unanswered question Roret et al, 2014). XDH1, in turn, belongs to the family of XORs and is a central player in purine catabolism.…”

Section: Grxs17 Associates With Fe-s Client Proteinsmentioning

confidence: 82%

Glutaredoxin GRXS17 Associates with the Cytosolic Iron-Sulfur Cluster Assembly Pathway

et al. 2016

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Cytosolic monothiol glutaredoxins (GRXs) are required in iron-sulfur (Fe-S) cluster delivery and iron sensing in yeast and mammals. In plants, it is unclear whether they have similar functions. Arabidopsis (Arabidopsis thaliana) has a sole class II cytosolic monothiol GRX encoded by GRXS17. Here, we used tandem affinity purification to establish that Arabidopsis GRXS17 associates with most known cytosolic Fe-S assembly (CIA) components. Similar to mutant plants with defective CIA components, grxs17 loss-of-function mutants showed some degree of hypersensitivity to DNA damage and elevated expression of DNA damage marker genes. We also found that several putative Fe-S client proteins directly bind to GRXS17, such as XANTHINE DEHYDROGENASE1 (XDH1), involved in the purine salvage pathway, and CYTOSOLIC THIOURIDYLASE SUBUNIT1 and CYTOSOLIC THIOURIDYLASE SUBUNIT2, both essential for the 2-thiolation step of 5-methoxycarbonylmethyl-2-thiouridine (mcm 5 s 2 U) modification of tRNAs. Correspondingly, profiling of the grxs17-1 mutant pointed to a perturbed flux through the purine degradation pathway and revealed that it phenocopied mutants in the elongator subunit ELO3, essential for the mcm 5 tRNA modification step, although we did not find XDH1 activity or tRNA thiolation to be markedly reduced in the grxs17-1 mutant. Taken together, our data suggest that plant cytosolic monothiol GRXs associate with the CIA complex, as in other eukaryotes, and contribute to, but are not essential for, the correct functioning of client Fe-S proteins in unchallenged conditions.

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“…2). For instance, the ISC factors Nfu1 and BolA3 appear to preferentially mature lipoate synthase and respiratory complexes I and II, while Ind1 seems to be specific for Fe/S cluster insertion into complex I (Bych et al, 2008;Cameron et al, 2011;Navarro-Sastre et al, 2011;Roret et al, 2014;Sheftel et al, 2009). …”

Section: Fe/s Proteinsmentioning

confidence: 97%