Journal ArticleDOI
Frataxin Acts as an Iron Chaperone Protein to Modulate Mitochondrial Aconitase Activity
Anne Laure Bulteau,Heather A. O'Neill,Mary Claire Kennedy,Masao Ikeda-Saito,Grazia Isaya,Luke I. Szweda +5 more
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TLDR
Frataxin is an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation and can undergo reversible citrate-dependent modulation in activity in response to pro-oxidants.Abstract:
Numerous degenerative disorders are associated with elevated levels of prooxidants and declines in mitochondrial aconitase activity. Deficiency in the mitochondrial iron-binding protein frataxin results in diminished activity of various mitochondrial iron-sulfur proteins including aconitase. We found that aconitase can undergo reversible citrate-dependent modulation in activity in response to pro-oxidants. Frataxin interacted with aconitase in a citrate-dependent fashion, reduced the level of oxidant-induced inactivation, and converted inactive [3Fe-4S]1+ enzyme to the active [4Fe-4S]2+ form of the protein. Thus, frataxin is an iron chaperone protein that protects the aconitase [4Fe-4S]2+ cluster from disassembly and promotes enzyme reactivation.read more
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Trinucleotide Repeat Disorders
Harry T. Orr,Huda Y. Zoghbi +1 more
TL;DR: It is exciting that within a span of 15 years, pathogenesis studies of this class of disorders are beginning to reveal pathways that are potential therapeutic targets.
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Mitochondria take center stage in aging and neurodegeneration
TL;DR: There is strong evidence from genetics and transgenic mouse models that mitochondrial dysfunction results in neurodegeneration and may contribute to the pathogenesis of Alzheimer’s disease, Parkinson's disease, Huntington's Disease, amyotrophic lateral sclerosis, hereditary spastic paraplegia, and cerebellar degenerations.
Journal ArticleDOI
Structure of the Hydrophilic Domain of Respiratory Complex I from Thermus thermophilus
TL;DR: The crystal structure of the hydrophilic domain (peripheral arm) of complex I from Thermus thermophilus has been solved at 3.3 angstrom resolution and reveals new aspects of the mechanism and evolution of the enzyme.
Journal ArticleDOI
Mitochondria, oxidative stress and neurodegeneration.
Antonio Federico,Elena Cardaioli,Paola Da Pozzo,Patrizia Formichi,Gian Nicola Gallus,Elena Radi +5 more
TL;DR: There is strong evidence that mitochondrial dysfunction occurs early and has a primary role in pathogenesis, and several mitochondrial diseases as models of neurodegeneration are discussed.
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Variable tandem repeats accelerate evolution of coding and regulatory sequences.
Rita Gemayel,Marcelo D. Vinces,Marcelo D. Vinces,Matthieu Legendre,Kevin J. Verstrepen,Kevin J. Verstrepen +5 more
TL;DR: An underestimated third class of genotypic variation: changes in microsatellite and minisatellite repeats is discussed, which combine characteristics of genetic and epigenetic changes that may facilitate organismal evolvability.
References
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Journal ArticleDOI
The inactivation of Fe-S cluster containing hydro-lyases by superoxide.
TL;DR: The working hypothesis is O2- inactivates these enzymes by oxidizing their clusters to an unstable oxidation state, and cluster degradation follows, and spinach dihydroxy-acid dehydratase, a member of the hydro-lyase class that has a catalytically active [2Fe-2S] cluster, is not inactivated and does not lose iron in the presence of O2.
Journal ArticleDOI
Oxidative damage during aging targets mitochondrial aconitase
TL;DR: It is shown that mitochondrial aconitase, an enzyme in the citric acid cycle, is a specific target of oxidative damage during aging of the housefly and allows for the assessment of the physiological age of a specific individual and provides a method for the evaluation of treatments designed to affect the aging process.
Journal ArticleDOI
Aconitase as iron-sulfur protein, enzyme, and iron-regulatory protein
TL;DR: Primary sequence data indicate the versatility of the aconitase fold in carrying out a 2370 Chemical Reviews, 1996, Vol.
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Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p.
TL;DR: By radiolabelling of yeast cells with 55Fe it is demonstrated that Isu1p binds an oxygen‐resistant non‐chelatable Fe/S cluster providing in vivo evidence for a scaffolding function of Isu 1p during Fe/s cluster assembly.
Journal ArticleDOI
Iron-sulfur cluster biosynthesis. Characterization of frataxin as an iron donor for assembly of [2Fe-2S] clusters in ISU-type proteins.
Taejin Yoon,James A. Cowan +1 more
TL;DR: This paper demonstrates human frataxin to bind from six to seven iron ions and demonstrates holo fratXin to form a complex with ISU with sub-micromolar binding affinities, suggesting an important role for iron in cross-linking the two proteins and/or stabilizing the structure of fratxin that is recognized by ISU.
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