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http://purl.uniprot.org/citations/22220943http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22220943http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/22220943http://purl.org/dc/terms/identifier"doi:10.1089/ars.2011.4265"xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/author"Swoboda P."xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/author"Navas P."xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/author"Miranda-Vizuete A."xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/author"Pedrajas J.R."xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/author"Link C.D."xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/author"Cabello J."xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/author"Fierro-Gonzalez J.C."xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/author"Cacho-Valadez B."xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/author"Munoz-Lobato F."xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/name"Antioxid Redox Signal"xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/pages"1384-1400"xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/title"The characterization of the Caenorhabditis elegans mitochondrial thioredoxin system uncovers an unexpected protective role of thioredoxin reductase 2 in beta-amyloid peptide toxicity."xsd:string
http://purl.uniprot.org/citations/22220943http://purl.uniprot.org/core/volume"16"xsd:string
http://purl.uniprot.org/citations/22220943http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/22220943
http://purl.uniprot.org/citations/22220943http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/22220943
http://purl.uniprot.org/uniprot/Q17424#attribution-A84893E5BE3C8ABE1205F09AEFA585AFhttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/22220943
http://purl.uniprot.org/uniprot/P30635#attribution-A84893E5BE3C8ABE1205F09AEFA585AFhttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/22220943
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http://purl.uniprot.org/uniprot/#_P11141-mappedCitation-22220943http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/22220943
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