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Title: The Characterization of the Caenorhabditis elegans Mitochondrial Thioredoxin System Uncovers an Unexpected Protective Role of Thioredoxin Reductase 2 in β-Amyloid Peptide Toxicity
Authors: Cacho-Valadez, Briseida; Muñoz-Lobato, Fernando; Pedrajas, José R.; Cabello, Juan; Fierro-González, Juan Carlos; Navas, Plácido; Swoboda, Peter; Link, Chris D.; Miranda-Vizuete, Antonio
Keywords: Mitochondrial thioredoxin system
Caenorhabditis elegans
Thioredoxin 2
Thioredoxin reductase 2
Protein
Oxygen
Apoptotic
Alzheimer's disease
Issue Date: 15-Feb-2012
Publisher: Mary Ann Liebert
Citation: Antioxidants and Redox Signalling 16(12): 1384-1400 (2012)
Abstract: [Aim]: Functional in vivo studies on the mitochondrial thioredoxin system are hampered by the embryonic or larval lethal phenotypes displayed by murine or Drosophila knock-out models. Thus, the access to alternative metazoan knock-out models for the mitochondrial thioredoxin system is of critical importance. [Results]: We report here the characterization of the mitochondrial thioredoxin system of Caenorhabditis elegans that is composed of the genes trx-2 and trxr-2. We demonstrate that the proteins thioredoxin 2 (TRX-2) and thioredoxin reductase 2 (TRXR-2) localize to the mitochondria of several cells and tissues of the nematode and that trx-2 and trxr-2 are upregulated upon induction of the mitochondrial unfolded protein response. Surprisingly, C. elegans trx-2 (lof ) and trxr-2 (null) single and double mutants are viable and display similar growth rates as wild-type controls. Moreover, the lack of the mitochondrial thioredoxin system does not affect longevity, reactive oxygen species production or the apoptotic program. Interestingly, we found a protective role of TRXR-2 in a transgenic nematode model of Alzheimer's disease (AD) that expresses human β-amyloid peptide and causes an age-dependent progressive paralysis. Hence, trxr-2 downregulation enhanced the paralysis phenotype, while a strong decrease of β-amyloid peptide and amyloid deposits occurred when TRXR-2 was overexpressed. [Innovation]: C. elegans provides the first viable metazoan knock-out model for the mitochondrial thioredoxin system and identifies a novel role of this system in β-amyloid peptide toxicity and AD. [Conclusion]: The nematode strains characterized in this work make C. elegans an ideal model organism to study the pathophysiology of the mitochondrial thioredoxin system at the level of a complete organism.
Publisher version (URL): http://dx.doi.org/10.1089/ars.2011.4265
URI: http://hdl.handle.net/10261/47087
DOI: 10.1089/ars.2011.4265
ISSN: 1523-0864
E-ISSN: 1557-7716
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1 - Cacho-Valadez main revised-2.docArtículo337,5 kBMicrosoft WordView/Open
2 - Cacho-Valadez Supplemental revised-2.docMaterial suplementario y método249 kBMicrosoft WordView/Open
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