Search results for "Iron-Sulfur Proteins"
showing 10 items of 15 documents
mRNA-binding protein tristetraprolin is essential for cardiac response to iron deficiency by regulating mitochondrial function
2018
Cells respond to iron deficiency by activating iron-regulatory proteins to increase cellular iron uptake and availability. However, it is not clear how cells adapt to conditions when cellular iron uptake does not fully match iron demand. Here, we show that the mRNA-binding protein tristetraprolin (TTP) is induced by iron deficiency and degrades mRNAs of mitochondrial Fe/S-cluster-containing proteins, specifically Ndufs1 in complex I and Uqcrfs1 in complex III, to match the decrease in Fe/S-cluster availability. In the absence of TTP, Uqcrfs1 levels are not decreased in iron deficiency, resulting in nonfunctional complex III, electron leakage, and oxidative damage. Mice with deletion of Ttp …
Transcriptional regulation of the proton translocating NADH dehydrogenase genes (nuoA-N) of Escherichia coli by electron acceptors, electron donors a…
1995
The promoter region and transcriptional regulation of the nuoA-N gene locus encoding the proton-translocating NADH:quinone oxidoreductase was analysed. A 560 bp intergenic region upstream of the nuo locus was followed by a gene (designated lrhA for LysR homologue A) coding for a gene regulator similar to those of the LysR family. Disruption of lrhA did not affect growth (respiratory or non-respiratory) or expression of nuo significantly. Transcriptional regulation of nuo by electron acceptors, electron donors and the transcriptional regulators ArcA, FNR, NarL and NarP, and by IHF (integration host factor) was studied with protein and operon fusions containing the promoter region up to base …
The elemental role of iron in DNA synthesis and repair
2017
Iron is an essential redox element that functions as a cofactor in many metabolic pathways. Critical enzymes in DNA metabolism, including multiple DNA repair enzymes (helicases, nucleases, glycosylases, demethylases) and ribonucleotide reductase, use iron as an indispensable cofactor to function. Recent striking results have revealed that the catalytic subunit of DNA polymerases also contains conserved cysteine-rich motifs that bind iron–sulfur (Fe/S) clusters that are essential for the formation of stable and active complexes. In line with this, mitochondrial and cytoplasmic defects in Fe/S cluster biogenesis and insertion into the nuclear iron-requiring enzymes involved in DNA synthesis a…
Reduced Apo-Fumarate Nitrate Reductase Regulator (ApoFNR) as the Major Form of FNR in Aerobically Growing Escherichia coli▿
2008
ABSTRACT Under anoxic conditions, the Escherichia coli oxygen sensor FNR (fumarate nitrate reductase regulator) is in the active state and contains a [4Fe-4S] cluster. Oxygen converts [4Fe-4S]FNR to inactive [2Fe-2S]FNR. After prolonged exposure to air in vitro, apoFNR lacking a Fe-S cluster is formed. ApoFNR can be differentiated from Fe-S-containing forms by the accessibility of the five Cys thiol residues, four of which serve as ligands for the Fe-S cluster. The presence of apoFNR in aerobically and anaerobically grown E. coli was analyzed in situ using thiol reagents. In anaerobically and aerobically grown cells, the membrane-permeable monobromobimane labeled one to two and four Cys res…
Regulatory O 2 tensions for the synthesis of fermentation products in Escherichia coli and relation to aerobic respiration
1997
In an oxystat, the synthesis of the fermentation products formate, acetate, ethanol, lactate, and succinate of Escherichia coli was studied as a function of the O2 tension (pO2) in the medium. The pO2 values that gave rise to half-maximal synthesis of the products (pO0. 5) were 0.2-0.4 mbar for ethanol, acetate, and succinate, and 1 mbar for formate. The pO0.5 for the expression of the adhE gene encoding alcohol dehydrogenase was approximately 0.8 mbar. Thus, the pO2 for the onset of fermentation was distinctly lower than that for anaerobic respiration (pO0.5/= 5 mbar), which was determined earlier. An essential role for quinol oxidase bd in microaerobic growth was demonstrated. A mutant de…
O2 as the regulatory signal for FNR-dependent gene regulation in Escherichia coli
1996
With an oxystat, changes in the pattern of expression of FNR-dependent genes from Escherichia coli were studied as a function of the O2 tension (pO2) in the medium. Expression of all four tested genes was decreased by increasing O2. However, the pO2 values that gave rise to half-maximal repression (pO(0.5)) were dependent on the particular promoter and varied between 1 and 5 millibars (1 bar = 10(5) Pa). The pO(0.5) value for the ArcA-regulated succinate dehydrogenase genes was in the same range (pO(0.5) = 4.6 millibars). At these pO2 values, the cytoplasm can be calculated to be well supplied with O2 by diffusion. Therefore, intracellular O2 could provide the signal to FNR, suggesting that…
The Friedreich's Ataxia protein frataxin modulates DNA base excision repair in prokaryotes and mammals
2010
DNA-repair mechanisms enable cells to maintain their genetic information by protecting it from mutations that may cause malignant growth. Recent evidence suggests that specific DNA-repair enzymes contain ISCs (iron–sulfur clusters). The nuclearencoded protein frataxin is essential for the mitochondrial biosynthesis of ISCs. Frataxin deficiency causes a neurodegenerative disorder named Friedreich's ataxia in humans. Various types of cancer occurring at young age are associated with this disease, and hence with frataxin deficiency. Mice carrying a hepatocyte-specific disruption of the frataxin gene develop multiple liver tumours for unresolved reasons. In the present study, we show that frata…
O2-sensing and O2-dependent gene regulation in facultatively anaerobic bacteria.
1995
Availability of O2 is one of the most important regulatory signals in facultatively anaerobic bacteria. Various two- or one-component sensor/regulator systems control the expression of aerobic and anaerobic metabolism in response to O2. Most of the sensor proteins contain heme or Fe as cofactors that interact with O2 either by binding or by a redox reaction. The ArcA/ArcB regulator of aerobic metabolism in Escherichia coli may use a different sensory mechanism. In two-component regulators, the sensor is located in the cytoplasmic membrane, whereas one-component regulators are located in the cytoplasm. Under most conditions, O2 can readily reach the cytoplasm and could provide the signal in …
Yeast Dun1 Kinase Regulates Ribonucleotide Reductase Inhibitor Sml1 in Response to Iron Deficiency
2014
Iron is an essential micronutrient for all eukaryotic organisms because it participates as a redox-active cofactor in many biological processes, including DNA replication and repair. Eukaryotic ribonucleotide reductases (RNRs) are Fe-dependent enzymes that catalyze deoxyribonucleoside diphosphate (dNDP) synthesis. We show here that the levels of the Sml1 protein, a yeast RNR large-subunit inhibitor, specifically decrease in response to both nutritional and genetic Fe deficiencies in a Dun1-dependent but Mec1/Rad53- and Aft1-independent manner. The decline of Sml1 protein levels upon Fe starvation depends on Dun1 forkhead-associated and kinase domains, the 26S proteasome, and the vacuolar pr…
Stimulation of Fe-S cluster insertion into apoFNR by Escherichia coli glutaredoxins 1, 2 and 3 in vitro.
2004
Abstract The oxygen sensor fumarate nitrate reductase regu-lator (FNR) of Escherichia coli contains in the active (anaerobic)state a [4Fe–4S] 2þ cluster which is lost after exposure to O 2 .Inaerobically prepared apoFNR, or in FNR obtained by treatmentof [4Fe–4S] FNR with O 2 in vitro, intramolecular cysteinedisulfides are found, including the cysteine residues which serveas ligands for the Fe–S cluster. It is shown here that thereconstitution of [4Fe–4S] FNR from this form of aerobicapoFNR was preceded by a long lag phase when glutathione wasused as the reducing agent. Addition of E. coli glutaredoxins(Grx) 1, 2 or 3 decreased the lag phase greatly and stimulatedthe reconstitution rate slig…