Mechanisms of iron–sulfur protein maturation in mitochondria, cytosol and nucleus of eukaryotes

Lill, Roland; Dutkiewicz, Rafał; Elsässer, Hans–Peter; Hausmann, Anja; Netz, Daili J. A.; Pierik, Antonio J.; Stehling, Oliver; Urzica, Eugen I.; Mühlenhoff, Ulrich

doi:10.1016/j.bbamcr.2006.05.011

Cited by 150 publications

(103 citation statements)

References 134 publications

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“…In eukaryotes, Fe/S proteins are localized in the mitochondria, cytosol and nucleus 9 . Strikingly, maturation of the extra-mitochondrial Fe/S proteins depends on the function of the mitochondrial ISC assembly machinery 10 .…”

Section: Introductionmentioning

confidence: 99%

Analysis of iron–sulfur protein maturation in eukaryotes

2009

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Section: Introductionmentioning

confidence: 99%

Analysis of iron–sulfur protein maturation in eukaryotes

2009

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“…More than 200 proteins require Fe-S clusters for their biological function, including members of the ETC complexes, enzymes, and several transcription factors to regulate gene expression. Moreover, Fe-S clusters can also act as sensors of iron and oxygen (4). Although the chemical structures of Fe-S clusters moieties appear simple, their biogenesis in a living cell is highly complex and coordinated process.…”

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confidence: 99%

Mapping Key Residues of ISD11 Critical for NFS1-ISD11 Subcomplex Stability

Saha

Srivastava

Kumar

et al. 2015

Journal of Biological Chemistry

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Background: NFS1-ISD11 complex is essential for the Fe-S cluster assembly process and the homozygous R68L ISD11 mutation causes the mitochondrial disorder, COXPD19. Results: Putative helix-3 and the C terminus of ISD11 are critical for NFS1-ISD11 subcomplex formation and Fe-S cluster biogenesis. Conclusion: ISD11 interaction is critical for NFS1 stability and its steady-state levels, in vivo. Significance: Identified important ISD11 residues will provides valuable information to understand COXPD19 progression.

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“…The CIA machinery comprises several proteins (10,11), among which one named Dre2 has been recently identified in yeast (12). The C-terminal domain of Dre2 (residues 228-348) is able to bind two ISCs, a [2Fe-2S] and a [4Fe-4S] (12,13).…”

mentioning

confidence: 99%

Molecular view of an electron transfer process essential for iron–sulfur protein biogenesis

Banci

Bertini

Calderone

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Biogenesis of iron-sulfur cluster proteins is a highly regulated process that requires complex protein machineries. In the cytosolic iron-sulfur protein assembly machinery, two human key proteins-NADPH-dependent diflavin oxidoreductase 1 (Ndor1) and anamorsinform a stable complex in vivo that was proposed to provide electrons for assembling cytosolic iron-sulfur cluster proteins. The Ndor1-anamorsin interaction was also suggested to be implicated in the regulation of cell survival/death mechanisms. In the present work we unravel the molecular basis of recognition between Ndor1 and anamorsin and of the electron transfer process. This is based on the structural characterization of the two partner proteins, the investigation of the electron transfer process, and the identification of those protein regions involved in complex formation and those involved in electron transfer. We found that an unstructured region of anamorsin is essential for the formation of a specific and stable protein complex with Ndor1, whereas the C-terminal region of anamorsin, containing the [2Fe-2S] redox center, transiently interacts through complementary charged residues with the FMN-binding site region of Ndor1 to perform electron transfer. Our results propose a molecular model of the electron transfer process that is crucial for understanding the functional role of this interaction in human cells.Fe/S protein maturation | CIAPIN1 domain | diflavin reductase I ron-sulfur clusters (ISCs) are ancient inorganic cofactors that are crucial for many protein functions in eukaryotic and bacterial cells (1-3). The clusters are composed of inorganic sulfide and ferric/ ferrous iron atoms, the latter being preferentially coordinated by cysteinyl residues (4-6). Because inorganic sulfide and ferrous/ferric iron atoms are toxic in vivo, biosynthesis of ISC proteins within cells is a highly regulated process that requires complex protein machineries for the mobilization of Fe and S atoms from appropriate sources, for their assembly into ISC forms and their final delivery to the recipient proteins (7-9). Three distinct protein machineries are operative and essential in the (nonplant) eukaryotic cells for the biogenesis of ISC proteins: (i) the ISC assembly machinery in the mitochondrial matrix, (ii) the ISC export machinery located in the mitochondrial intermembrane space, and (iii) the cytosolic iron-sulfur protein assembly (CIA) machinery.The CIA machinery comprises several proteins (10, 11), among which one named Dre2 has been recently identified in yeast (12). The C-terminal domain of Dre2 (residues 228-348) is able to bind two ISCs, a [2Fe-2S] and a [4Fe-4S] (12, 13). The [2Fe-2S] cluster of Dre2 receives electrons from a cytosolic diflavin reductase, termed Tah18 (13), which contains a FAD and a FMN prosthetic group, respectively, bound in two distinct structural domains, to accept electrons from NADPH (14). Dre2 and Tah18 are protein partners forming a stable complex in vivo (13, 15). The C-terminal region of Dre2 (residues 173-348) is fundamenta...

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Mechanisms of iron–sulfur protein maturation in mitochondria, cytosol and nucleus of eukaryotes

Cited by 150 publications

References 134 publications

Analysis of iron–sulfur protein maturation in eukaryotes

Analysis of iron–sulfur protein maturation in eukaryotes

Mapping Key Residues of ISD11 Critical for NFS1-ISD11 Subcomplex Stability

Molecular view of an electron transfer process essential for iron–sulfur protein biogenesis

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