Cytosolic Fe-S Cluster Protein Maturation and Iron Regulation Are Independent of the Mitochondrial Erv1/Mia40 Import System

Ozer, Hatice Kubra; Dlouhy, Adrienne C.; Thornton, Jeremy; Hu, Jingjing; Liu, Yilin; Barycki, Joseph J.; Balk, Janneke; Outten, Caryn E.

doi:10.1074/jbc.m115.682179

Cited by 19 publications

(11 citation statements)

References 59 publications

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“…The export of this structure is mediated by ABCB7 in cooperation with ALR, an FAD-dependent sulfhydryl oxidase. The implication of ALR is, however, still a matter of debate, as a study in yeast could not show impaired cytosolic iron–sulfur cluster assembly [ 6 ]. The mitochondrial machinery can synthesize [2Fe–2S] or [4Fe–4S] clusters and incorporate these into the appropriate apoproteins (Fig.…”

Section: Mitochondrial Iron–sulfur Biosynthesis (Isc)mentioning

confidence: 99%

Clinical and genetic aspects of defects in the mitochondrial iron–sulfur cluster synthesis pathway

Vanlander

Coster

2018

J Biol Inorg Chem

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Iron–sulfur clusters are evolutionarily conserved biological structures which play an important role as cofactor for multiple enzymes in eukaryotic cells. The biosynthesis pathways of the iron–sulfur clusters are located in the mitochondria and in the cytosol. The mitochondrial iron–sulfur cluster biosynthesis pathway (ISC) can be divided into at least twenty enzymatic steps. Since the description of frataxin deficiency as the cause of Friedreich’s ataxia, multiple other deficiencies in ISC biosynthesis pathway have been reported. In this paper, an overview is given of the clinical, biochemical and genetic aspects reported in humans affected by a defect in iron–sulfur cluster biosynthesis.

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Section: Mitochondrial Iron–sulfur Biosynthesis (Isc)mentioning

confidence: 99%

Clinical and genetic aspects of defects in the mitochondrial iron–sulfur cluster synthesis pathway

Vanlander

Coster

2018

J Biol Inorg Chem

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“…Interestingly, glutathione production in the prothoracic gland is also required for steroidogenesis (Enya et al, 2017 ). The possibility that glutathione supports Fe-S cluster biosynthesis in this tissue should be considered (Song et al, 2006 ; Auchère et al, 2008 ; Qi et al, 2013 ; Ozer et al, 2015 ).…”

Section: Fe-s and Moco Enzymesmentioning

confidence: 99%

Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life Cycle by Controlling Cell Metabolism

2018

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Iron sulfur (Fe-S) clusters and the molybdenum cofactor (Moco) are present at enzyme sites, where the active metal facilitates electron transfer. Such enzyme systems are soluble in the mitochondrial matrix, cytosol and nucleus, or embedded in the inner mitochondrial membrane, but virtually absent from the cell secretory pathway. They are of ancient evolutionary origin supporting respiration, DNA replication, transcription, translation, the biosynthesis of steroids, heme, catabolism of purines, hydroxylation of xenobiotics, and cellular sulfur metabolism. Here, Fe-S cluster and Moco biosynthesis in Drosophila melanogaster is reviewed and the multiple biochemical and physiological functions of known Fe-S and Moco enzymes are described. We show that RNA interference of Mocs3 disrupts Moco biosynthesis and the circadian clock. Fe-S-dependent mitochondrial respiration is discussed in the context of germ line and somatic development, stem cell differentiation and aging. The subcellular compartmentalization of the Fe-S and Moco assembly machinery components and their connections to iron sensing mechanisms and intermediary metabolism are emphasized. A biochemically active Fe-S core complex of heterologously expressed fly Nfs1, Isd11, IscU, and human frataxin is presented. Based on the recent demonstration that copper displaces the Fe-S cluster of yeast and human ferredoxin, an explanation for why high dietary copper leads to cytoplasmic iron deficiency in flies is proposed. Another proposal that exosomes contribute to the transport of xanthine dehydrogenase from peripheral tissues to the eye pigment cells is put forward, where the Vps16a subunit of the HOPS complex may have a specialized role in concentrating this enzyme within pigment granules. Finally, we formulate a hypothesis that (i) mitochondrial superoxide mobilizes iron from the Fe-S clusters in aconitase and succinate dehydrogenase; (ii) increased iron transiently displaces manganese on superoxide dismutase, which may function as a mitochondrial iron sensor since it is inactivated by iron; (iii) with the Krebs cycle thus disrupted, citrate is exported to the cytosol for fatty acid synthesis, while succinyl-CoA and the iron are used for heme biosynthesis; (iv) as iron is used for heme biosynthesis its concentration in the matrix drops allowing for manganese to reactivate superoxide dismutase and Fe-S cluster biosynthesis to reestablish the Krebs cycle.

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“… Sipos et al (2002) demonstrated in their work that while proteins with iron-sulfur clusters can be assembled under anaerobic conditions in the mitochondria of S. cerevisiae, maturation of iron-sulfur proteins in its cytosol requires the presence of glutathione even if the media is maintained anaerobic. It has been shown that glutathione protects iron-sulfur proteins from oxidative stress, thereby allowing for their successful maturation ( Ozer et al, 2015 ). Therefore, ADP1 cells were induced for ER synthesis under anaerobic conditions in the presence of 1 mM glutathione for 12 h, followed by incubation under anaerobic or aerobic conditions.…”

Section: Resultsmentioning

confidence: 99%

Biocatalytic production of adipic acid from glucose using engineered Saccharomyces cerevisiae

Raj

Partow

Correia

et al. 2018

Metabolic Engineering Communications

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Adipic acid is an important industrial chemical used in the synthesis of nylon-6,6. The commercial synthesis of adipic acid uses petroleum-derived benzene and releases significant quantities of greenhouse gases. Biocatalytic production of adipic acid from renewable feedstocks could potentially reduce the environmental damage and eliminate the need for fossil fuel precursors. Recently, we have demonstrated the first enzymatic hydrogenation of muconic acid to adipic acid using microbial enoate reductases (ERs) - complex iron-sulfur and flavin containing enzymes. In this work, we successfully expressed the Bacillus coagulans ER in a Saccharomyces cerevisiae strain producing muconic acid and developed a three-stage fermentation process enabling the synthesis of adipic acid from glucose. The ability to express active ERs and significant acid tolerance of S. cerevisiae highlight the applicability of the developed yeast strain for the biocatalytic production of adipic acid from renewable feedstocks.

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Cytosolic Fe-S Cluster Protein Maturation and Iron Regulation Are Independent of the Mitochondrial Erv1/Mia40 Import System

Cited by 19 publications

References 59 publications

Clinical and genetic aspects of defects in the mitochondrial iron–sulfur cluster synthesis pathway

Clinical and genetic aspects of defects in the mitochondrial iron–sulfur cluster synthesis pathway

Iron Sulfur and Molybdenum Cofactor Enzymes Regulate the Drosophila Life Cycle by Controlling Cell Metabolism

Biocatalytic production of adipic acid from glucose using engineered Saccharomyces cerevisiae

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