Iron–sulfur cluster biosynthesis and trafficking – impact on human disease conditions

Wachnowsky, Christine; Fidai, Insiya; Cowan, J. A.

doi:10.1039/c7mt00180k

Cited by 72 publications

(82 citation statements)

References 227 publications

(252 reference statements)

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“…This biosynthesis process is accomplished by the so‐called iron–sulfur‐cluster assembly (ISC) machinery of mitochondria. ISC is responsible for the biogenesis of iron–sulfur proteins both within and outside the organelle . In the model of Fe/S protein biogenesis in mitochondria proposed by Lill et al , during the second step of biogenesis the monothiol glutaredoxin Grx5 helps to transfer the Fe/S cluster toward apoproteins, presumably via transient binding of the Fe/S cluster in a glutathione‐containing complex.…”

Section: Subcellular Compartmentalizationmentioning

confidence: 99%

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

et al. 2018

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Glutathione is considered the major non‐protein low molecular weight modulator of redox processes and the most important thiol reducing agent of the cell. The biosynthesis of glutathione occurs in the cytosol from its constituent amino acids, but this tripeptide is also present in the most important cellular districts, such as mitochondria, nucleus, and endoplasmic reticulum, thus playing a central role in several metabolic pathways and cytoprotection mechanisms. Indeed, glutathione is involved in the modulation of various cellular processes and, not by chance, it is a ubiquitous determinant for redox signaling, xenobiotic detoxification, and regulation of cell cycle and death programs. The balance between its concentration and redox state is due to a complex series of interactions between biosynthesis, utilization, degradation, and transport. All these factors are of great importance to understand the significance of cellular redox balance and its relationship with physiological responses and pathological conditions. The purpose of this review is to give an overview on glutathione cellular compartmentalization. Information on its subcellular distribution provides a deeper understanding of glutathione‐dependent processes and reflects the importance of compartmentalization in the regulation of specific cellular pathways. © 2018 BioFactors, 45(2):152–168, 2019

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Section: Subcellular Compartmentalizationmentioning

confidence: 99%

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

et al. 2018

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“…Mitochondria serve important roles in the regulation of a wide variety of intracellular processes, including providing a source of ATP energy, generating reactive oxygen species ( 18 , 19 ), and regulating intracellular Ca 2+ homeostasis ( 20 ), iron-sulfur protein assembly ( 21 , 22 ), apoptosis ( 23 - 25 ) and mitophagy ( 26 , 27 ). During cell reprogramming and cellular transformation, mitochondria undergo dynamic changes ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Dynamic influence of Rhein lysinate on HeLa cells

et al. 2018

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In a previous study, it was demonstrated that Rhein lysinate (RHL) inhibited HeLa cell proliferation via a specific mechanism. The aim of the present study was to clarify the mechanism of RHL by investigating its effect on mitochondrial damage and cell apoptosis. The results indicated that RHL inhibited cell growth and proliferation in HeLa cells. HeLa cells treated with RHL developed extensive vacuolization in a dose- and time-dependent manner. Ultrastructure analysis using transmission electron microscopy revealed that the vacuoles observed were damaged mitochondria and endoplasmic reticulum. The effects of RHL on mitochondria were further confirmed by a decrease in mitochondrial membrane potential and increased generation of reactive oxygen species. The mitochondrial proteome was analyzed, and the results demonstrated that the expression of the cytoskeletal protein keratin and dermal papilla derived protein 12 (associated with the oxidation- reduction process), which are associated with mitochondrial structure and function, were decreased compared with the untreated control group. Hoechst staining, flow cytometry and western blotting also revealed that apoptosis was induced at 24 h following RHL treatment. These results confirm that RHL toxicity in HeLa cells is a dynamic process. Vacuolar degeneration appeared in HeLa cells treated with 160 µmol/l RHL during the first 6 h and with the extension of RHL treatment, cell apoptosis was presented at ~24 h in HeLa cells.

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“…The iron donor protein frataxin (FXN) provides the iron atom, and the sulfur is delivered by the desulfurase complex consisting of the cysteine desulfurase NFS1 and LYRM4 (ISD11). Following further maturation, the ISCU/HSC20/HSPA9 complex facilitates the transfer of Fe-S clusters to their targets (for a review, see Reference [230]). Yeast LYRM4 mutants (ISD11) with abolished LYR motif have partially impaired Nfs1 function and are prone to aggregation.…”

Section: The Role Of Mtacp and Lyrm Proteins In Fe-s Cluster Biogenesismentioning

confidence: 99%

Mitochondrial OXPHOS Biogenesis: Co-Regulation of Protein Synthesis, Import, and Assembly Pathways

Tang

Thompson

Taylor

et al. 2020

IJMS

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The assembly of mitochondrial oxidative phosphorylation (OXPHOS) complexes is an intricate process, which—given their dual-genetic control—requires tight co-regulation of two evolutionarily distinct gene expression machineries. Moreover, fine-tuning protein synthesis to the nascent assembly of OXPHOS complexes requires regulatory mechanisms such as translational plasticity and translational activators that can coordinate mitochondrial translation with the import of nuclear-encoded mitochondrial proteins. The intricacy of OXPHOS complex biogenesis is further evidenced by the requirement of many tightly orchestrated steps and ancillary factors. Early-stage ancillary chaperones have essential roles in coordinating OXPHOS assembly, whilst late-stage assembly factors—also known as the LYRM (leucine–tyrosine–arginine motif) proteins—together with the mitochondrial acyl carrier protein (ACP)—regulate the incorporation and activation of late-incorporating OXPHOS subunits and/or co-factors. In this review, we describe recent discoveries providing insights into the mechanisms required for optimal OXPHOS biogenesis, including the coordination of mitochondrial gene expression with the availability of nuclear-encoded factors entering via mitochondrial protein import systems.

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Iron–sulfur cluster biosynthesis and trafficking – impact on human disease conditions

Cited by 72 publications

References 227 publications

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

Dynamic influence of Rhein lysinate on HeLa cells

Mitochondrial OXPHOS Biogenesis: Co-Regulation of Protein Synthesis, Import, and Assembly Pathways

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