Glutathione revisited: a vital function in iron metabolism and ancillary role in thiol-redox control.
Chitranshu Kumar,Aeid Igbaria,Benoît D'Autréaux,Anne-Gaëlle Planson,Christophe Junot,Emmanuel Godat,Anand K. Bachhawat,Agnès Delaunay-Moisan,Michel B. Toledano +8 more
TLDR
It is proposed that glutathione is essential by its requirement in ISC assembly, but only serves as a thioredoxin backup in cytosolic thiol‐redox maintenance, a model challenging the traditional view of it as prime actor in thiol-redox control.Abstract:
Glutathione contributes to thiol-redox control and to extra-mitochondrial iron–sulphur cluster (ISC) maturation. To determine the physiological importance of these functions and sort out those that account for the GSH requirement for viability, we performed a comprehensive analysis of yeast cells depleted of or containing toxic levels of GSH. Both conditions triggered an intense iron starvation-like response and impaired the activity of extra-mitochondrial ISC enzymes but did not impact thiol-redox maintenance, except for high glutathione levels that altered oxidative protein folding in the endoplasmic reticulum. While iron partially rescued the ISC maturation and growth defects of GSH-depleted cells, genetic experiments indicated that unlike thioredoxin, glutathione could not support by itself the thiol-redox duties of the cell. We propose that glutathione is essential by its requirement in ISC assembly, but only serves as a thioredoxin backup in cytosolic thiol-redox maintenance. Glutathione-high physiological levels are thus meant to insulate its cytosolic function in iron metabolism from variations of its concentration during redox stresses, a model challenging the traditional view of it as prime actor in thiol-redox control.read more
Citations
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Glutathione Homeostasis and Functions: Potential Targets forMedical Interventions
TL;DR: The principal mechanisms of the protective role of GSH against reactive species and electrophiles are characterized and a hypothesis for investigation of the physiology and biochemistry of glutathione is provided with a focus on human and animal health.
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The role of mitochondria in cellular iron–sulfur protein biogenesis and iron metabolism ☆
Roland Lill,Bastian Hoffmann,Sabine Molik,Antonio J. Pierik,Nicole Rietzschel,Oliver Stehling,Marta A. Uzarska,Holger Webert,Claudia Wilbrecht,Ulrich Mühlenhoff +9 more
TL;DR: Fe/S protein biogenesis and cellular iron metabolism are tightly linked to coordinate iron supply and utilization.
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The Metabolic Underpinnings of Ferroptosis.
Jiashuo Zheng,Marcus Conrad +1 more
TL;DR: There has been overwhelming interest in the last few years aiming for a better molecular understanding of the ferroptotic death process, which emerges to be the root cause of a number of diseases.
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Are reactive oxygen species always detrimental to pathogens
TL;DR: This study reviews the classic infections that are controlled by ROS and the cases in which ROS appear as promoters of infection, challenging the paradigm, and discusses the possible mechanisms by which ROS could promote particular infections.
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Thioredoxin and glutaredoxin systems in plants: molecular mechanisms, crosstalks, and functional significance
Yves Meyer,Christophe Belin,Valérie Delorme-Hinoux,Jean-Philippe Reichheld,Christophe Riondet +4 more
TL;DR: Interestingly, recent development integrating biochemical analysis, proteomic data, and genetics have revealed an extensive crosstalk between the cytosolic NTR/Trx and GSH/Grx systems, which reveals the high plasticity of the redox systems in plants.
References
More filters
Journal ArticleDOI
Genomic expression programs in the response of yeast cells to environmental changes.
Audrey P. Gasch,Paul T. Spellman,Camilla M. Kao,Orna Carmel-Harel,Michael B. Eisen,Gisela Storz,David Botstein,Patrick O. Brown +7 more
TL;DR: Analysis of genomic expression patterns in the yeast Saccharomyces cerevisiae implicated the transcription factors Yap1p, as well as Msn2p and Msn4p, in mediating specific features of the transcriptional response, while the identification of novel sequence elements provided clues to novel regulators.
Journal ArticleDOI
Protein S-nitrosylation: purview and parameters.
Douglas T. Hess,Akio Matsumoto,Sung Oog Kim,Harvey E. Marshall,Jonathan S. Stamler,Jonathan S. Stamler +5 more
TL;DR: S-nitrosylation conveys a large part of the ubiquitous influence of nitric oxide on cellular signal transduction, and provides a mechanism for redox-based physiological regulation.
Journal ArticleDOI
Functional and Genomic Analyses Reveal an Essential Coordination between the Unfolded Protein Response and ER-Associated Degradation
Kevin J. Travers,Christopher K Patil,Lisa Wodicka,David J. Lockhart,Jonathan S. Weissman,Peter Walter +5 more
TL;DR: The unfolded protein response and ERAD are dynamic responses required for the coordinated disposal of misfolded proteins even in the absence of acute stress.
Journal ArticleDOI
Function and biogenesis of iron–sulphur proteins
TL;DR: This work has shown that different biogenesis machineries in both bacteria and eukaryotes have been discovered that assist Fe–S-protein maturation according to uniform biosynthetic principles.
Journal ArticleDOI
A Thiol Peroxidase Is an H2O2 Receptor and Redox-Transducer in Gene Activation
TL;DR: The glutathione peroxidase-like enzyme Gpx3 is identified as a second component of the pathway, serving the role of sensor and transducer of the hydroperoxide signal to Yap1, revealing a redox-signaling function for a GPx- like enzyme and elucidate a eukaryotic Hydroperoxide-sensing mechanism.