Fe-S Cluster Biogenesis in Isolated Mammalian Mitochondria

Pandey, Alok; Pain, Jayashree; Ghosh, Arnab K.; Dancis, Andrew; Pain, Debkumar

doi:10.1074/jbc.m114.610402

Cited by 27 publications

(14 citation statements)

References 64 publications

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“…The reasons why this occurs and how the PANK2 deficiency is involved are still obscure. Very recent data, obtained on isolated mammalian mitochondria, demonstrated that ISC biosynthesis requires, other than iron and sulphur, also GTP, NADH and ATP ( Pandey et al, 2015 ). A very reliable hypothesis could be that the impairment of the Krebs cycle due to CoA deficiency might result in lower production of GTP and NADH, with the consequent partial iron utilisation in ISC biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial iron and energetic dysfunction distinguish fibroblasts and induced neurons from pantothenate kinase-associated neurodegeneration patients

Santambrogio

Dusi

Guaraldo

et al. 2015

Neurobiology of Disease

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Pantothenate kinase-associated neurodegeneration is an early onset autosomal recessive movement disorder caused by mutation of the pantothenate kinase-2 gene, which encodes a mitochondrial enzyme involved in coenzyme A synthesis. The disorder is characterised by high iron levels in the brain, although the pathological mechanism leading to this accumulation is unknown. To address this question, we tested primary skin fibroblasts from three patients and three healthy subjects, as well as neurons induced by direct fibroblast reprogramming, for oxidative status, mitochondrial functionality and iron parameters. The patients' fibroblasts showed altered oxidative status, reduced antioxidant defence, and impaired cytosolic and mitochondrial aconitase activities compared to control cells. Mitochondrial iron homeostasis and functionality analysis of patient fibroblasts indicated increased labile iron pool content and reactive oxygen species development, altered mitochondrial shape, decreased membrane potential and reduced ATP levels. Furthermore, analysis of induced neurons, performed at a single cell level, confirmed some of the results obtained in fibroblasts, indicating an altered oxidative status and signs of mitochondrial dysfunction, possibly due to iron mishandling. Thus, for the first time, altered biological processes have been identified in vitro in live diseased neurons. Moreover, the obtained induced neurons can be considered a suitable human neuronal model for the identification of candidate therapeutic compounds for this disease.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial iron and energetic dysfunction distinguish fibroblasts and induced neurons from pantothenate kinase-associated neurodegeneration patients

Santambrogio

Dusi

Guaraldo

et al. 2015

Neurobiology of Disease

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“…The persulfides, which are also intermediates in the synthesis of particular sulfur biomolecules [30,31], are nowadays being considered candidate species for the transduction of the signals triggered by H 2 S. Not only are these species suggested to be more nucleophilic and acidic than the original thiols, but they also show an electrophilic character that is lacking in the original thiols [32]. In addition, enzymatic pathways for the H 2 S–independent formation of persulfides have been reported [33,34,35,36,37,38,39,40,41,42].…”

Section: Persulfides As Potential Transducers Of H2s Signalingmentioning

confidence: 99%

Hydrogen Sulfide and Persulfides Oxidation by Biologically Relevant Oxidizing Species

et al. 2019

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Hydrogen sulfide (H2S/HS–) can be formed in mammalian tissues and exert physiological effects. It can react with metal centers and oxidized thiol products such as disulfides (RSSR) and sulfenic acids (RSOH). Reactions with oxidized thiol products form persulfides (RSSH/RSS–). Persulfides have been proposed to transduce the signaling effects of H2S through the modification of critical cysteines. They are more nucleophilic and acidic than thiols and, contrary to thiols, also possess electrophilic character. In this review, we summarize the biochemistry of hydrogen sulfide and persulfides, focusing on redox aspects. We describe biologically relevant one- and two-electron oxidants and their reactions with H2S and persulfides, as well as the fates of the oxidation products. The biological implications are discussed.

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“…In the last 15 years, increasing efforts have been dedicated to understand the mechanism of iron-sulfur cluster biogenesis because this is an essential machine common to all organisms which increasingly appears to have an important role in human disease. Precious new information was obtained by studies in cellular or animal models, such as yeast, drosophila (Kondapalli et al, 2008 ) and mice (Pandey et al, 2015 ). In vitro studies, which work with a well-defined number of highly purified components, have nevertheless remained essential to clarify the role of each of the players and understand the chemistry which drives cluster formation.…”

Section: Discussionmentioning

confidence: 99%

A New Tessera into the Interactome of the isc Operon: A Novel Interaction between HscB and IscS

Puglisi

Yan

Adinolfi

et al. 2016

Front. Mol. Biosci.

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Iron sulfur clusters are essential universal prosthetic groups which can be formed inorganically but, in biology, are bound to proteins and produced enzymatically. Most of the components of the machine that produces the clusters are conserved throughout evolution. In bacteria, they are encoded in the isc operon. Previous reports provide information on the role of specific components but a clear picture of how the whole machine works is still missing. We have carried out a study of the effects of the co-chaperone HscB from the model system E. coli. We document a previously undetected weak interaction between the chaperone HscB and the desulfurase IscS, one of the two main players of the machine. The binding site involves a region of HscB in the longer stem of the approximately L-shaped molecule, whereas the interacting surface of IscS overlaps with the surface previously involved in binding other proteins, such as ferredoxin and frataxin. Our findings provide an entirely new perspective to our comprehension of the role of HscB and propose this protein as a component of the IscS complex.

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Fe-S Cluster Biogenesis in Isolated Mammalian Mitochondria

Cited by 27 publications

References 64 publications

Mitochondrial iron and energetic dysfunction distinguish fibroblasts and induced neurons from pantothenate kinase-associated neurodegeneration patients

Mitochondrial iron and energetic dysfunction distinguish fibroblasts and induced neurons from pantothenate kinase-associated neurodegeneration patients

Hydrogen Sulfide and Persulfides Oxidation by Biologically Relevant Oxidizing Species

A New Tessera into the Interactome of the isc Operon: A Novel Interaction between HscB and IscS

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