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1.
J Inorg Biochem ; 255: 112535, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38527404

RESUMO

Human mitoNEET (mNT) and CISD2 are two NEET proteins characterized by an atypical [2Fe-2S] cluster coordination involving three cysteines and one histidine. They act as redox switches with an active state linked to the oxidation of their cluster. In the present study, we show that reduced glutathione but also free thiol-containing molecules such as ß-mercaptoethanol can induce a loss of the mNT cluster under aerobic conditions, while CISD2 cluster appears more resistant. This disassembly occurs through a radical-based mechanism as previously observed with the bacterial SoxR. Interestingly, adding cysteine prevents glutathione-induced cluster loss. At low pH, glutathione can bind mNT in the vicinity of the cluster. These results suggest a potential new regulation mechanism of mNT activity by glutathione, an essential actor of the intracellular redox state.


Assuntos
Proteínas Ferro-Enxofre , Humanos , Proteínas Ferro-Enxofre/química , Oxirredução , Compostos de Sulfidrila , Cisteína/metabolismo , Glutationa/metabolismo , Homeostase , Proteínas Mitocondriais/química
2.
Med Sci (Paris) ; 40(2): 203-205, 2024 Feb.
Artigo em Francês | MEDLINE | ID: mdl-38411431

RESUMO

Title: La glutathionylation de la protéine mitochondriale humaine MIA40 régule l'homéostasie des ROS. Abstract: Dans le cadre du module d'enseignement « Physiopathologie de la signalisation ¼ proposé par l'université Paris-Saclay, les étudiants du Master « Biologie Santé ¼ se sont confrontés à l'écriture scientifique. Ils ont sélectionné des articles scientifiques dans le domaine de la signalisation cellulaire présentant des résultats originaux, via des approches expérimentales variées, sur des thèmes allant de l'exploration des sites de contacts membranaires aux mécanismes moléculaires de la ferroptose, en passant par la signalisation hépatique et tumorale. Après un travail préparatoire réalisé avec l'équipe pédagogique, les étudiants, organisés en binômes/trinômes, ont ensuite rédigé, guidés par des chercheurs, une Nouvelle soulignant les résultats majeurs et l'originalité de l'article étudié. Ils ont beaucoup apprécié cette initiation à l'écriture d'articles scientifiques et, comme vous pourrez le lire, se sont investis dans ce travail avec enthousiasme !


Assuntos
Espécies Reativas de Oxigênio , Humanos
3.
J Biol Chem ; 300(3): 105745, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38354784

RESUMO

The NEET proteins, an important family of iron-sulfur (Fe-S) proteins, have generated a strong interest due to their involvement in diverse diseases such as cancer, diabetes, and neurodegenerative disorders. Among the human NEET proteins, CISD3 has been the least studied, and its functional role is still largely unknown. We have investigated the biochemical features of CISD3 at the atomic and in cellulo levels upon challenge with different stress conditions i.e., iron deficiency, exposure to hydrogen peroxide, and nitric oxide. The redox and cellular stability properties of the protein agree on a predominance of reduced form of CISD3 in the cells. Upon the addition of iron chelators, CISD3 loses its Fe-S clusters and becomes unstructured, and its cellular level drastically decreases. Chemical shift perturbation measurements suggest that, upon cluster oxidation, the protein undergoes a conformational change at the C-terminal CDGSH domain, which determines the instability of the oxidized state. This redox-associated conformational change may be the source of cooperative electron transfer via the two [Fe2S2] clusters in CISD3, which displays a single sharp voltammetric signal at -31 mV versus SHE. Oxidized CISD3 is particularly sensitive to the presence of hydrogen peroxide in vitro, whereas only the reduced form is able to bind nitric oxide. Paramagnetic NMR provides clear evidence that, upon NO binding, the cluster is disassembled but iron ions are still bound to the protein. Accordingly, in cellulo CISD3 is unaffected by oxidative stress induced by hydrogen peroxide but it becomes highly unstable in response to nitric oxide treatment.


Assuntos
Proteínas Ferro-Enxofre , Óxido Nítrico , Humanos , Óxido Nítrico/metabolismo , Peróxido de Hidrogênio/metabolismo , Proteínas Ferro-Enxofre/metabolismo , Ferro/metabolismo , Estresse Oxidativo , Oxirredução
4.
Proc Natl Acad Sci U S A ; 121(5): e2308776121, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38252831

RESUMO

We present a drug design strategy based on structural knowledge of protein-protein interfaces selected through virus-host coevolution and translated into highly potential small molecules. This approach is grounded on Vinland, the most comprehensive atlas of virus-human protein-protein interactions with annotation of interacting domains. From this inspiration, we identified small viral protein domains responsible for interaction with human proteins. These peptides form a library of new chemical entities used to screen for replication modulators of several pathogens. As a proof of concept, a peptide from a KSHV protein, identified as an inhibitor of influenza virus replication, was translated into a small molecule series with low nanomolar antiviral activity. By targeting the NEET proteins, these molecules turn out to be of therapeutic interest in a nonalcoholic steatohepatitis mouse model with kidney lesions. This study provides a biomimetic framework to design original chemistries targeting cellular proteins, with indications going far beyond infectious diseases.


Assuntos
Influenza Humana , Vírus , Animais , Camundongos , Humanos , Proteoma , Peptídeos/farmacologia , Descoberta de Drogas
5.
Genes (Basel) ; 14(4)2023 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-37107536

RESUMO

Redox homeostasis is an equilibrium between reducing and oxidizing reactions within cells. It is an essential, dynamic process, which allows proper cellular reactions and regulates biological responses. Unbalanced redox homeostasis is the hallmark of many diseases, including cancer or inflammatory responses, and can eventually lead to cell death. Specifically, disrupting redox balance, essentially by increasing pro-oxidative molecules and favouring hyperoxidation, is a smart strategy to eliminate cells and has been used for cancer treatment, for example. Selectivity between cancer and normal cells thus appears crucial to avoid toxicity as much as possible. Redox-based approaches are also employed in the case of infectious diseases to tackle the pathogens specifically, with limited impacts on host cells. In this review, we focus on recent advances in redox-based strategies to fight eukaryotic pathogens, especially fungi and eukaryotic parasites. We report molecules recently described for causing or being associated with compromising redox homeostasis in pathogens and discuss therapeutic possibilities.


Assuntos
Doenças Transmissíveis , Eucariotos , Oxirredução , Fungos/metabolismo
6.
Cancers (Basel) ; 14(19)2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36230784

RESUMO

Auranofin (Ridaura®, AUF) is a gold complex originally approved as an antirheumatic agent that has emerged as a potential candidate for multiple repurposed therapies. The best-studied anticancer mechanism of AUF is the inhibition of thioredoxin reductase (TrxR). However, a number of reports indicate a more complex and multifaceted mode of action for AUF that could be cancer cell type- and dose-dependent. In this study, we observed that AUF displayed variable cytotoxicity in five triple-negative breast cancer cell lines. Using representative MDA-MB-231 cells treated with moderate and cytotoxic doses of AUF, we evidenced that an AUF-mediated TrxR inhibition alone may not be sufficient to induce cell death. Cytotoxic doses of AUF elicited rapid and drastic intracellular oxidative stress affecting the mitochondria, cytoplasm and nucleus. A "redoxome" proteomics investigation revealed that a short treatment with a cytotoxic dose AUF altered the redox state of a number of cysteines-containing proteins, pointing out that the cell proliferation/cell division/cell cycle and cell-cell adhesion/cytoskeleton structure were the mostly affected pathways. Experimentally, AUF treatment triggered a dose-dependent S-phase arrest and a rapid disintegration of the actin cytoskeleton structure. Our study shows a new spectrum of AUF-induced early effects and should provide novel insights into the complex redox-based mechanisms of this promising anticancer molecule.

7.
Biomolecules ; 12(2)2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35204772

RESUMO

Size Exclusion Chromatography coupled with Multi-Angle Light Scattering (SEC-MALS) is a technique that determines the absolute molar mass (molecular weight) of macromolecules in solution, such as proteins or polymers, by detecting their light scattering intensity. Because SEC-MALS does not rely on the assumption of the globular state of the analyte and the calibration of standards, the molar mass can be obtained for proteins of any shape, as well as for intrinsically disordered proteins and aggregates. Yet, corrections need to be made for samples that absorb light at the wavelength of the MALS laser, such as iron-sulfur [Fe-S] cluster-containing proteins. We analyze several examples of [2Fe-2S] and [4Fe-4S] cluster-containing proteins, for which various corrections were applied to determine the absolute molar mass of both the apo- and holo-forms. Importantly, the determination of the absolute molar mass of the [2Fe-2S]-containing holo-NEET proteins allowed us to ascertain a change in the oligomerization state upon cluster binding and, thus, to highlight one essential function of the cluster.


Assuntos
Luz , Proteínas , Cromatografia em Gel , Peso Molecular , Proteínas/química , Espalhamento de Radiação
8.
Biomedicines ; 9(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34440194

RESUMO

Mitochondrial proteins carrying iron-sulfur (Fe-S) clusters are involved in essential cellular pathways such as oxidative phosphorylation, lipoic acid synthesis, and iron metabolism. NFU1, BOLA3, IBA57, ISCA2, and ISCA1 are involved in the last steps of the maturation of mitochondrial [4Fe-4S]-containing proteins. Since 2011, mutations in their genes leading to five multiple mitochondrial dysfunction syndromes (MMDS types 1 to 5) were reported. The aim of this systematic review is to describe all reported MMDS-patients. Their clinical, biological, and radiological data and associated genotype will be compared to each other. Despite certain specific clinical elements such as pulmonary hypertension or dilated cardiomyopathy in MMDS type 1 or 2, respectively, nearly all of the patients with MMDS presented with severe and early onset leukoencephalopathy. Diagnosis could be suggested by high lactate, pyruvate, and glycine levels in body fluids. Genetic analysis including large gene panels (Next Generation Sequencing) or whole exome sequencing is needed to confirm diagnosis.

9.
Biochemistry ; 60(31): 2419-2424, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34310123

RESUMO

The human mitochondrial protein, mitoNEET (mNT), belongs to the family of small [2Fe-2S] NEET proteins that bind their iron-sulfur clusters with a novel and characteristic 3Cys:1His coordination motif. mNT has been implicated in the regulation of lipid and glucose metabolisms, iron/reactive oxygen species homeostasis, cancer, and possibly Parkinson's disease. The geometric structure of mNT as a function of redox state and pH is critical for its function. In this study, we combine 57Fe nuclear resonance vibrational spectroscopy with density functional theory calculations to understand the novel properties of this important protein.


Assuntos
Cisteína/química , Ferro/química , Lisina/química , Proteínas Mitocondriais/química , Enxofre/química , Teoria da Densidade Funcional , Humanos , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Ligação Proteica , Domínios Proteicos , Vibração
10.
G3 (Bethesda) ; 11(7)2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34009341

RESUMO

B-type eukaryotic polymerases contain a [4Fe-4S] cluster in their C-terminus domain, whose role is not fully understood yet. Among them, DNA polymerase delta (Polδ) plays an essential role in chromosomal DNA replication, mostly during lagging strand synthesis. Previous in vitro work suggested that the Fe-S cluster in Polδ is required for efficient binding of the Pol31 subunit, ensuring stability of the Polδ complex. Here, we analyzed the in vivo consequences resulting from an impaired coordination of the Fe-S cluster in Polδ. We show that a single substitution of the very last cysteine coordinating the cluster by a serine is responsible for the generation of massive DNA damage during S phase, leading to checkpoint activation, requirement of homologous recombination for repair, and ultimately to cell death when the repair capacities of the cells are overwhelmed. These data indicate that impaired Fe-S cluster coordination in Polδ is responsible for aberrant replication. More generally, Fe-S in Polδ may be compromised by various stress including anti-cancer drugs. Possible in vivo Polδ Fe-S cluster oxidation and collapse may thus occur, and we speculate this could contribute to induced genomic instability and cell death, comparable to that observed in pol3-13 cells.


Assuntos
DNA Polimerase III , Proteínas de Saccharomyces cerevisiae , DNA Polimerase III/genética , DNA Polimerase III/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Replicação do DNA/genética , Dano ao DNA
11.
Biomedicines ; 9(4)2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33916457

RESUMO

Human CISD2 and mitoNEET are two NEET proteins anchored in the endoplasmic reticulum and mitochondria membranes respectively, with an Fe-S containing domain stretching out in the cytosol. Their cytosolic domains are close in sequence and structure. In the present study, combining cellular and biochemical approaches, we compared both proteins in order to possibly identify specific roles and mechanisms of action in the cell. We show that both proteins exhibit a high intrinsic stability and a sensitivity of their cluster to oxygen. In contrast, they differ in according to expression profiles in tissues and intracellular half-life. The stability of their Fe-S cluster and its ability to be transferred in vitro are affected differently by pH variations in a physiological and pathological range for cytosolic pH. Finally, we question a possible role for CISD2 in cellular Fe-S cluster trafficking. In conclusion, our work highlights unexpected major differences in the cellular and biochemical features between these two structurally close NEET proteins.

12.
Med Sci (Paris) ; 37(4): 397-399, 2021 Apr.
Artigo em Francês | MEDLINE | ID: mdl-33908859

RESUMO

TITLE: La protéine MDM2 favorise la mort cellulaire en affectant la bioénergétique mitochondriale. ABSTRACT: Pour la sixième année, dans le cadre du module d'enseignement « Physiopathologie de la signalisation ¼ proposé par l'université Paris-sud, les étudiants du Master « Biologie Santé ¼ de l'université Paris-Saclay se sont confrontés à l'écriture scientifique. Ils ont sélectionné une quinzaine d'articles scientifiques récents dans le domaine de la signalisation cellulaire présentant des résultats originaux, via des approches expérimentales variées, sur des thèmes allant des relations hôte-pathogène aux innovations thérapeutiques, en passant par la signalisation hépatique et le métabolisme. Après un travail préparatoire réalisé avec l'équipe pédagogique, les étudiants, organisés en binômes, ont ensuite rédigé, guidés par des chercheurs, une Nouvelle soulignant les résultats majeurs et l'originalité de l'article étudié. Ils ont beaucoup apprécié cette initiation à l'écriture d'articles scientifiques et, comme vous pourrez le lire, se sont investis dans ce travail avec enthousiasme ! Trois de ces Nouvelles sont publiées dans ce numéro, les autres le seront dans des prochains numéros.


Assuntos
Morte Celular/fisiologia , Metabolismo Energético/fisiologia , Mitocôndrias/metabolismo , NADH Desidrogenase/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Respiração Celular/fisiologia , Humanos , Neoplasias/metabolismo
13.
Free Radic Biol Med ; 162: 533-541, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33232753

RESUMO

Malaria, caused by protozoan parasites, is a major public health issue in subtropical countries. An arsenal of antimalarial treatments is available, however, resistance is spreading, calling for the development of new antimalarial compounds. The new lead antimalarial drug plasmodione is a redox-active compound that impairs the redox balance of parasites leading to cell death. Based on extensive in vitro assays, a model of its mode of action was drawn, involving the generation of active plasmodione metabolites that act as subversive substrates of flavoproteins, initiating a redox cycling process producing reactive oxygen species. We showed that, in yeast, the mitochondrial respiratory chain NADH-dehydrogenases are the main redox-cycling target enzymes. Furthermore, our data supported the proposal that plasmodione is a pro-drug acting via its benzhydrol and benzoyl metabolites. Here, we selected plasmodione-resistant yeast mutants to further decipher plasmodione mode of action. Of the eleven mutants analysed, nine harboured a mutation in the FAD binding subunit of succinate dehydrogenase (SDH). The analysis of the SDH mutations points towards a specific role for SDH-bound FAD in plasmodione bioactivation, possibly in the first step of the process, highlighting a novel property of SDH.


Assuntos
Antimaláricos , Malária , Succinato Desidrogenase , Antimaláricos/farmacologia , Malária/tratamento farmacológico , Oxirredução , Saccharomyces cerevisiae , Succinato Desidrogenase/genética , Vitamina K 3/análogos & derivados
15.
Free Radic Biol Med ; 141: 269-278, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31238126

RESUMO

Malaria is caused by protozoan parasites and remains a major public health issue in subtropical areas. Plasmodione (3-[4-(trifluoromethyl)benzyl]-menadione) is a novel early lead compound displaying fast-acting antimalarial activity. Treatment with this redox active compound disrupts the redox balance of parasite-infected red blood cells. In vitro, the benzoyl analogue of plasmodione can act as a subversive substrate of the parasite flavoprotein NADPH-dependent glutathione reductase, initiating a redox cycling process producing ROS. Whether this is also true in vivo remains to be investigated. Here, we used the yeast model to investigate the mode of action of plasmodione and uncover enzymes and pathways involved in its activity. We showed that plasmodione is a potent inhibitor of yeast respiratory growth, that in drug-treated cells, the ROS-sensitive aconitase was impaired and that cells with a lower oxidative stress defence were highly sensitive to the drug, indicating that plasmodione may act via an oxidative stress. We found that the mitochondrial respiratory chain flavoprotein NADH-dehydrogenases play a key role in plasmodione activity. Plasmodione and metabolites act as substrates of these enzymes, the reaction resulting in ROS production. This in turn would damage ROS-sensitive enzymes leading to growth arrest. Our data further suggest that plasmodione is a pro-drug whose activity is mainly mediated by its benzhydrol and benzoyl metabolites. Our results in yeast are coherent with existing data obtained in vitro and in Plasmodium falciparum, and provide additional hypotheses that should be investigated in parasites.


Assuntos
Antimaláricos/farmacologia , Malária/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Vitamina K 3/análogos & derivados , Vitamina K 3/farmacologia , Animais , Transporte de Elétrons/efeitos dos fármacos , Flavoproteínas Transferidoras de Elétrons/genética , Eritrócitos/efeitos dos fármacos , Glutationa Redutase/genética , Humanos , Malária/parasitologia , Oxirredução/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/patogenicidade , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética
16.
Biochemistry ; 57(38): 5616-5628, 2018 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-30204426

RESUMO

Human mitoNEET (mNT) is the first identified Fe-S protein of the mammalian outer mitochondrial membrane. Recently, we demonstrated the involvement of mNT in a specific cytosolic pathway dedicated to the reactivation of oxidatively damaged cytosolic aconitase by cluster transfer. In vitro studies using apo-ferredoxin (FDX) reveal that mNT uses an Fe-based redox switch mechanism to regulate the transfer of its cluster. Using the "gold standard" cluster recipient protein, FDX, we show that this transfer is direct and that only one of the two mNT clusters is transferred when the second one is decomposed. Combining complementary biophysical and biochemical approaches, we show that pH affects both the sensitivity of the cluster to O2 and dimer stability. Around physiological cytosolic pH, the ability of mNT to transfer its cluster is tightly regulated by the pH. Finally, mNT is extremely resistant to H2O2 compared to ISCU and SufB, two other Fe-S cluster transfer proteins, which is consistent with its involvement in a repair pathway of stress-damaged Fe-S proteins. Taken together, our results suggest that the ability of mNT to transfer its cluster to recipient proteins is not only controlled by the redox state of its cluster but also tightly modulated by the pH of the cytosol. We propose that when pathophysiological conditions such as cancer and neurodegenerative diseases dysregulate cellular pH homeostasis, this pH-dependent regulation of mNT is lost, as is the regulation of cellular pathways under the control of mNT.


Assuntos
Ferredoxinas/metabolismo , Peróxido de Hidrogênio/metabolismo , Proteínas Ferro-Enxofre/metabolismo , Ferro/metabolismo , Proteínas Mitocondriais/metabolismo , Enxofre/metabolismo , Ferredoxinas/química , Humanos , Concentração de Íons de Hidrogênio , Proteínas Ferro-Enxofre/química , Proteínas Mitocondriais/química , Oxirredução , Multimerização Proteica
18.
PLoS One ; 13(3): e0194782, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29596470

RESUMO

Biogenesis of iron-sulfur clusters (ISC) is essential to almost all forms of life and involves complex protein machineries. This process is initiated within the mitochondrial matrix by the ISC assembly machinery. Cohort and case report studies have linked mutations in ISC assembly machinery to severe mitochondrial diseases. The voltage-dependent anion channel (VDAC) located within the mitochondrial outer membrane regulates both cell metabolism and apoptosis. Recently, the C-terminal truncation of the VDAC1 isoform, termed VDAC1-ΔC, has been observed in chemoresistant late-stage tumor cells grown under hypoxic conditions with activation of the hypoxia-response nuclear factor HIF-1α. These cells harbored atypical enlarged mitochondria. Here, we show for the first time that depletion of several proteins of the mitochondrial ISC machinery in normoxia leads to a similar enlarged mitochondria phenotype associated with accumulation of VDAC1-ΔC. This truncated form of VDAC1 accumulates in the absence of HIF-1α and HIF-2α activations and confers cell resistance to drug-induced apoptosis. Furthermore, we show that when hypoxia and siRNA knock-down of the ISC machinery core components are coupled, the cell phenotype is further accentuated, with greater accumulation of VDAC1-ΔC. Interestingly, we show that hypoxia promotes the downregulation of several proteins (ISCU, NFS1, FXN) involved in the early steps of mitochondrial Fe-S cluster biogenesis. Finally, we have identified the mitochondria-associated membrane (MAM) localized Fe-S protein CISD2 as a link between ISC machinery downregulation and accumulation of anti-apoptotic VDAC1-ΔC. Our results are the first to associate dysfunction in Fe-S cluster biogenesis with cleavage of VDAC1, a form which has previously been shown to promote tumor resistance to chemotherapy, and raise new perspectives for targets in cancer therapy.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ferro/metabolismo , Mitocôndrias/metabolismo , Deleção de Sequência , Enxofre/metabolismo , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Caspase 3/metabolismo , Ativação Enzimática/genética , Técnicas de Silenciamento de Genes , Células HeLa , Células Hep G2 , Humanos , Mitocôndrias/efeitos dos fármacos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteólise/efeitos dos fármacos , Hipóxia Tumoral/efeitos dos fármacos , Canal de Ânion 1 Dependente de Voltagem/genética
20.
Methods Enzymol ; 595: 83-106, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28882209

RESUMO

MitoNEET is the first identified Fe-S protein anchored to mammalian outer mitochondrial membranes with the vast majority of the protein polypeptide located in the cytosol, including its [2Fe-2S] cluster-binding domain. The coordination of the cluster is unusual and involves three cysteines and one histidine. MitoNEET is capable of transferring its redox-active Fe-S cluster to a bacterial apo-ferredoxin in vitro even under aerobic conditions, unlike other Fe-S transfer proteins such as ISCU. This specificity suggests its possible involvement in Fe-S repair after oxidative and/or nitrosative stress. Recently, we identified cytosolic aconitase/iron regulatory protein 1 (IRP1) as the first physiological protein acceptor of the mitoNEET Fe-S cluster in an Fe-S repair process. This chapter describes methods to study in vitro mitoNEET Fe-S cluster transfer/repair to a bacterial ferredoxin used as a model aporeceptor and in a more comprehensive manner to cytosolic aconitase/IRP1 after a nitrosative stress using in vitro, in cellulo, and in vivo methods.


Assuntos
Aconitato Hidratase/metabolismo , Proteína 1 Reguladora do Ferro/metabolismo , Proteínas Ferro-Enxofre/metabolismo , Ferro/metabolismo , Proteínas Mitocondriais/metabolismo , Aconitato Hidratase/química , Animais , Cisteína/metabolismo , Citosol/enzimologia , Escherichia coli , Ferredoxinas/metabolismo , Histidina/metabolismo , Humanos , Ferro/química , Proteína 1 Reguladora do Ferro/química , Proteínas Ferro-Enxofre/química , Membranas Mitocondriais/metabolismo , Estresse Nitrosativo , Oxirredução
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