論文 - 詳細
RRC ID | 17484 |
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著者 | Cacho-Valadez B, Muñoz-Lobato F, Pedrajas JR, Cabello J, Fierro-González JC, Navas P, Swoboda P, Link CD, Miranda-Vizuete A. |
タイトル | The characterization of the Caenorhabditis elegans mitochondrial thioredoxin system uncovers an unexpected protective role of thioredoxin reductase 2 in β-amyloid peptide toxicity. |
ジャーナル | Antioxid Redox Signal |
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. |
巻・号 | 16(12) |
ページ | 1384-400 |
公開日 | 2012-6-15 |
DOI | 10.1089/ars.2011.4265 |
PMID | 22220943 |
PMC | PMC3329951 |
MeSH | Amyloid beta-Peptides / genetics Amyloid beta-Peptides / metabolism* Amyloid beta-Peptides / toxicity* Animals Animals, Genetically Modified Apoptosis Caenorhabditis elegans / genetics Humans Mitochondria / metabolism* Real-Time Polymerase Chain Reaction Thioredoxin Reductase 2 / genetics Thioredoxin Reductase 2 / metabolism* Thioredoxins / genetics Thioredoxins / metabolism* Unfolded Protein Response |
IF | 7.04 |
引用数 | 25 |
WOS 分野 | ENDOCRINOLOGY & METABOLISM BIOCHEMISTRY & MOLECULAR BIOLOGY |
リソース情報 | |
線虫 | tm2047 tm2720 |