The Role of Heme and Iron-Sulfur Clusters in Mitochondrial Biogenesis, Maintenance, and Decay with Age

2002 ◽  
Vol 397 (2) ◽  
pp. 345-353 ◽  
Author(s):  
Hani Atamna ◽  
Patrick B Walter ◽  
Bruce N Ames
Keyword(s):  
Mitochondrial Biogenesis ◽  
Iron Sulfur Clusters ◽  
Iron Sulfur

The role of iron-sulfur clusters, S-adenosylmethionine, and radicals in the reaction of lysine 2,3-aminomutase

1995 ◽  
Vol 59 (2-3) ◽  
pp. 291
Author(s):  
P.A. Frey ◽  
M.D. Ballinger ◽  
G.H. Reed ◽  
R. LoBrutto ◽  
K. Lieder ◽  
...  
Keyword(s):  
Iron Sulfur Clusters ◽  
Iron Sulfur

Crucial Role of Conserved Cysteine Residues in the Assembly of Two Iron−Sulfur Clusters on the CIA Protein Nar1

Biochemistry ◽  
2009 ◽  
Vol 48 (22) ◽  
pp. 4946-4958 ◽  
Author(s):  
Eugen Urzica ◽  
Antonio J. Pierik ◽  
Ulrich Mühlenhoff ◽  
Roland Lill
Keyword(s):  
Crucial Role ◽  
Cysteine Residues ◽  
Iron Sulfur Clusters ◽  
Iron Sulfur

scholarly journals Role of XDHC in Molybdenum Cofactor Insertion into Xanthine Dehydrogenase of Rhodobacter capsulatus

1999 ◽  
Vol 181 (9) ◽  
pp. 2745-2751 ◽  
Author(s):  
Silke Leimkühler ◽  
Werner Klipp
Keyword(s):  
Flavin Adenine Dinucleotide ◽  
Rhodobacter Capsulatus ◽  
Strain Analysis ◽  
Transcriptional Regulator ◽  
Xanthine Dehydrogenase ◽  
Molybdenum Cofactor ◽  
Iron Sulfur Clusters ◽  
Iron Sulfur ◽  
A Subunit

ABSTRACT Rhodobacter capsulatus xanthine dehydrogenase (XDH) is composed of two subunits, XDHA and XDHB. Immediately downstream ofxdhB, a third gene was identified, designatedxdhC, which is cotranscribed with xdhAB. Interposon mutagenesis revealed that the xdhC gene product is required for XDH activity. However, XDHC is not a subunit of active XDH, which forms an α2β2 heterotetramer inR. capsulatus. It was shown that XDHC neither is a transcriptional regulator for xdh gene expression nor influences XDH stability. To analyze the function of XDHC for XDH inR. capsulatus, inactive XDH was purified from anxdhC mutant strain. Analysis of the molybdenum cofactor content of this enzyme demonstrated that in the absence of XDHC, no molybdopterin cofactor MPT is present in the XDHAB tetramer. In contrast, absorption spectra of inactive XDH isolated from thexdhC mutant revealed the presence of iron-sulfur clusters and flavin adenine dinucleotide, demonstrating that XDHC is not required for the insertion of these cofactors. The absence of MPT from XDH isolated from an xdhC mutant indicates that XDHC either acts as a specific MPT insertase or might be a specific chaperone facilitating the insertion of MPT and/or folding of XDH during or after cofactor insertion.

Special Delivery: The Role of Iron Chaperones in the Distribution of Iron in Developing Red Cells

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. SCI-45-SCI-45
Author(s):  
Caroline C. Philpott ◽  
Avery G Frey ◽  
Moon-Suhn Ryu ◽  
Daniel Palenchar ◽  
Justin Wildemann ◽  
...  
Keyword(s):  
Heme Iron ◽  
Human Cells ◽  
Erythroid Cell ◽  
Iron Sulfur Clusters ◽  
Non Heme Iron ◽  
Iron Sulfur ◽  
Iron Enzymes ◽  
Dinuclear Iron ◽  
Iron Delivery

Abstract Iron is an essential nutrient for every cell in the human body, yet it can also be a potent cellular toxin. Iron is essential because enzymes that require iron co-factors (namely, heme, iron-sulfur clusters, mononuclear and diiron centers) are involved in virtually every major metabolic process in the cell. Hundreds of iron, zinc, copper, and manganese proteins are expressed in human cells, yet little is known about the mechanisms by which these metalloproteins acquire their native metal ligands and avoid mis-metallation. Significant advances have been made in understanding the delivery of iron to iron-dependent enzymes in the cytosol. Poly(rC)-binding proteins (PCBPs) are multifunctional adaptors that mediate interactions between single-stranded nucleic acids, iron cofactors, and other proteins, affecting the fate and activity of the components of these interactions. PCBP1 is an iron-binding protein that delivers iron to ferritin in human cells via a direct protein-protein interaction and can be described as an iron chaperone. PCBP2, a human paralog of PCBP1, is also involved in the delivery of iron to ferritin, both in yeast cells and in human cells, suggesting that PCBP1 and PCBP2 work together in iron delivery. PCBP1 and PCBP2 can also deliver iron to the two major families of non-heme iron enzymes: the mononuclear and dinuclear iron-dependent oxygenases. The prolyl hydroxylases (PHDs) are mononuclear iron enzymes that regulate the degradation of hypoxia inducible factor 1 (HIF1). Misregulation of the HIF transcription factors leads to the development of a variety of cancers in humans. Cells depend on the iron chaperones PCBP1 and PCBP2 to maintain iron in the enzymatic active site of PHDs and the related enzyme, asparagyl hydroxylase and to maintain proper regulation of HIF1a, especially under conditions of iron limitation. Deoxyhypusine hydroxylase (DOHH) is a dinuclear iron enzyme that is required for the posttranslational modification of a single lysine residue on eukaryotic initiation factor 5A (eIF5A). EIF5A and the conversion of this conserved lysine to hypusine are essential in all eukaryotes, as it enables the translation of peptides containing polyproline sequences. We found that cells depleted of PCBP1 or PCBP2 exhibited reduced activity of DOHH, which was due to a loss of iron in the active site of the enzyme. Thus, PCBPs are basic components of a cytosolic iron delivery system that serves both of the major classes of non-heme iron enzymes in the cytosol. Recent work has indicated that a second type of iron delivery system in the cytosol is mediated by a monothiol glutaredoxin, Glrx3, which, in vitro, can bind and transfer iron-sulfur clusters to recipient apo-iron-sulfur proteins. We have determined that PCBP1 directly interacts with Glrx3-containing complexes and can affect the coordination of iron-sulfur clusters by Glrx3. The huge flux of iron through the developing erythroid cell represents unique challenges for the utilization of cellular iron. We have examined the role of PCBPs as iron chaperones in terminal erythroid differentiation. The role of ferritin in erythroid cell maturation is controversial, but our data indicate that ferritin, PCBPs and NCOA4 are critical factors in erythrocyte development. The flux of iron through ferritin via the lysosome appears to be critical for the transfer of iron to mitochondria for heme synthesis. Disclosures No relevant conflicts of interest to declare.

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