Formation of [4Fe-4S] Clusters in the Mitochondrial Iron–Sulfur Cluster Assembly Machinery

2014 ◽  
Vol 136 (46) ◽  
pp. 16240-16250 ◽  
Author(s):  
Diego Brancaccio ◽  
Angelo Gallo ◽  
Maciej Mikolajczyk ◽  
Kairit Zovo ◽  
Peep Palumaa ◽  
...  
Keyword(s):  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
Mitochondrial Iron

Multiple Causes of Iron Overload In Tissues, Cells and Subcellular Compartments

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. SCI-27-SCI-27
Author(s):  
Tracey Rouault
Keyword(s):  
Iron Overload ◽  
Iron Metabolism ◽  
Iron Uptake ◽  
Iron Homeostasis ◽  
Regulatory Protein ◽  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
Mitochondrial Iron

Abstract Abstract SCI-27 Iron metabolism is regulated in mammals to assure that adequate iron is delivered to the hematopoietic system to support erythropoiesis. In systemic iron metabolism, regulation of both iron uptake from the diet and release from erythrophagocytosing macrophages is coordinated by action of the peptide hormone, hepcidin, which inhibits activity of the iron exporter, ferroportin. In general, high expression of hepcidin diminishes duodenal iron uptake and reduces macrophage iron release, a combination observed in the anemia of chronic disease. Low expression of hepcidin, which is synthesized by hepatocytes and influenced by transferrin receptor 2, HFE, hemojuvelin and bone morphogenetic receptors, facilitates iron uptake. Mutations affecting genes in the hepcidin pathway cause hemochromatosis, characterized by systemic iron overload that affects mainly hepatocytes and cardiac myocytes, but spares the CNS. In contrast, there are several degenerative diseases of the CNS in which neuronal iron overload is prominent and may play a causal role. The underlying pathophysiologies of neuronal brain iron accumulation syndromes remain unclear, even though several causal genes have been identified, including pantothenate kinase 2 and aceruloplasminemia. In some cases, increased iron may be inaccessible, and cells may suffer from functional iron insufficiency, as we propose for animals that lack iron regulatory protein 2. It is also possible that errors in subcellular iron metabolism can lead to mitochondrial iron overload and concomitant cytosolic iron deficiency, a combination observed in Friedreich ataxia, ISCU myopathy, and the sideroblastic anemia caused by glutaredoxin 5 deficiency. In each of these diseases, mitochondrial iron-sulfur cluster assembly is impaired, and it appears that normal regulation of mitochondrial iron homeostasis depends on intact iron-sulfur cluster assembly. Finally, in heme oxygenase 1 deficient animals, macrophages in the spleen and liver die upon erythrophagocytosis, and failure to normally metabolize heme leads to shift of heme iron to proximal tubules and macrophages of the kidney. Thus, treatment of “iron overload” must depend on the underlying causes, and removal of iron is appropriate in hemochromatosis, but more specific forms of therapy are needed for other forms of iron overload. 1. Ye, H. & Rouault, T. A. (2010). Human iron-sulfur cluster assembly, cellular iron homeostasis, and disease. Biochemistry 49, 4945–4956. 2. Zhang, A. S. & Enns, C. A. (2009). Molecular mechanisms of normal iron homeostasis. Hematology Am Soc Hematol Educ Program 207–214. 3. Ye, H., Jeong, S. Y., Ghosh, M. C., Kovtunovych, G., Silvestri, L., Ortillo, D., Uchida, N., Tisdale, J., Camaschella, C. & Rouault, T. A. (2010). Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts. J Clin Invest 120, 1749–1761. 4. Ghosh, M. C., Tong, W. H., Zhang, D., Ollivierre-Wilson, H., Singh, A., Krishna, M. C., Mitchell, J. B. & Rouault, T. A. (2008). Tempol-mediated activation of latent iron regulatory protein activity prevents symptoms of neurodegenerative disease in IRP2 knockout mice. Proc Natl Acad Sci U S A 105, 12028–12033. 5. Crooks, D. R., Ghosh, M. C., Haller, R. G., Tong, W. H. & Rouault, T. A. (2010). Posttranslational stability of the heme biosynthetic enzyme ferrochelatase is dependent on iron availability and intact iron-sulfur cluster assembly machinery. Blood 115, 860–869. Disclosures: No relevant conflicts of interest to declare.

Functional analysis of Arabidopsis genes involved in mitochondrial iron–sulfur cluster assembly

2007 ◽  
Vol 64 (3) ◽  
pp. 225-240 ◽  
Author(s):  
Ana Paula Guedes Frazzon ◽  
Melissa V. Ramirez ◽  
Ujwala Warek ◽  
Janneke Balk ◽  
Jeverson Frazzon ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
Mitochondrial Iron

Defects in Mitochondrial Iron–Sulfur Cluster Assembly Induce Cysteine S-Polythiolation on Iron–Sulfur Apoproteins

2016 ◽  
Vol 25 (1) ◽  
pp. 28-40 ◽  
Author(s):  
Stefan Christ ◽  
Lars I. Leichert ◽  
Anna Willms ◽  
Roland Lill ◽  
Ulrich Mühlenhoff
Keyword(s):  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
Mitochondrial Iron

scholarly journals Architecture of the Human Mitochondrial Iron-Sulfur Cluster Assembly Machinery

2016 ◽  
Vol 291 (40) ◽  
pp. 21296-21321 ◽  
Author(s):  
Oleksandr Gakh ◽  
Wasantha Ranatunga ◽  
Douglas Y. Smith ◽  
Eva-Christina Ahlgren ◽  
Salam Al-Karadaghi ◽  
...  
Keyword(s):  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
Mitochondrial Iron

scholarly journals Architecture of the Yeast Mitochondrial Iron-Sulfur Cluster Assembly Machinery

2016 ◽  
Vol 291 (19) ◽  
pp. 10378-10398 ◽  
Author(s):  
Wasantha Ranatunga ◽  
Oleksandr Gakh ◽  
Belinda K. Galeano ◽  
Douglas Y. Smith ◽  
Christopher A. G. Söderberg ◽  
...  
Keyword(s):  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
Mitochondrial Iron

scholarly journals Multiple Sense and Antisense Promoters Contribute to the Regulated Expression of the isc-suf Operon for Iron-Sulfur Cluster Assembly in Rhodobacter

2019 ◽  
Vol 7 (12) ◽  
pp. 671 ◽  
Author(s):  
Xin Nie ◽  
Bernhard Remes ◽  
Gabriele Klug
Keyword(s):  
Rhodobacter Sphaeroides ◽  
Photosynthetic Electron Transport ◽  
Regulatory Proteins ◽  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Iron Sulfur Clusters ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
Photosynthetic Complexes ◽  
The One

A multitude of biological functions relies on iron-sulfur clusters. The formation of photosynthetic complexes goes along with an additional demand for iron-sulfur clusters for bacteriochlorophyll synthesis and photosynthetic electron transport. However, photooxidative stress leads to the destruction of iron-sulfur clusters, and the released iron promotes the formation of further reactive oxygen species. A balanced regulation of iron-sulfur cluster synthesis is required to guarantee the supply of this cofactor, on the one hand, but also to limit stress, on the other hand. The phototrophic alpha-proteobacterium Rhodobacter sphaeroides harbors a large operon for iron-sulfur cluster assembly comprising the iscRS and suf genes. IscR (iron-sulfur cluster regulator) is an iron-dependent regulator of isc-suf genes and other genes with a role in iron metabolism. We applied reporter gene fusions to identify promoters of the isc-suf operon and studied their activity alone or in combination under different conditions. Gel-retardation assays showed the binding of regulatory proteins to individual promoters. Our results demonstrated that several promoters in a sense and antisense direction influenced isc-suf expression and the binding of the IscR, Irr, and OxyR regulatory proteins to individual promoters. These findings demonstrated a complex regulatory network of several promoters and regulatory proteins that helped to adjust iron-sulfur cluster assembly to changing conditions in Rhodobacter sphaeroides.

scholarly journals Regulation of the HscA ATPase Reaction Cycle by the Co-chaperone HscB and the Iron-Sulfur Cluster Assembly Protein IscU

2004 ◽  
Vol 279 (52) ◽  
pp. 53924-53931 ◽  
Author(s):  
Jonathan J. Silberg ◽  
Tim L. Tapley ◽  
Kevin G. Hoff ◽  
Larry E. Vickery
Keyword(s):  
Cluster Assembly ◽  
Iron Sulfur Cluster ◽  
Reaction Cycle ◽  
Sulfur Cluster ◽  
Iron Sulfur ◽  
Atpase Reaction
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