Cited by 192Redox biology and oxidative stressMitochondrial Function and PathologyCell death mechanisms and regulation

Human Mitochondrial Thioredoxin

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Damdimopoulos, Anastasios E., Miranda-Vizuete, Antonio, Pelto-Huikko, Markku, Gustafsson, Jan-Åke, Spyrou, Giannis·2002·Journal of Biological Chemistry

Abstract

Thioredoxins (Trx) are a class of small multifunctional redox-active proteins found in all organisms. Recently, we reported the cloning of a mitochondrial thioredoxin, Trx2, from rat heart. To investigate the biological role of Trx2 we have isolated the human homologue, hTrx2, and generated HEK-293 cells overexpressing Trx2 (HEK-Trx2). Here, we show that HEK-Trx2 cells are more resistant toward etoposide. In addition, HEK-Trx2 are more sensitive toward rotenone, an inhibitor of complex I of the respiratory chain. Finally, overexpression of Trx2 confers an increase in mitochondrial membrane potential, DeltaPsi(m). Treatment with oligomycin could both reverse the effect of rotenone and decrease the membrane potential suggesting that Trx2 interferes with the activity of ATP synthase. Taken together, these results suggest that Trx2 interacts with specific components of the mitochondrial respiratory chain and plays an important role in the regulation of the mitochondrial membrane potential.

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Authors
Damdimopoulos, A. E., Miranda-Vizuete, A., Pelto-Huikko, M., Gustafsson, J.-Å., & Spyrou, G.
Affiliations
Karolinska Institutet (SE)
Corresponding author
Spyrou, Giannis
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-09
Volume
277
Issue
36
Pages
33249-33257
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2072623280
Cited by
192
References
1
Citations by year
2025: 1 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 3 · 2020: 8 · 2019: 6 · 2018: 2 · 2017: 5 · 2016: 7 · 2015: 2 · 2014: 11 · 2013: 5 · 2012: 13
FWCI
4.88
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
mitochondrial thioredoxin, Trx2, human homologue, redox proteins, etoposide resistance, rotenone, mitochondrial complex I inhibition, mitochondrial membrane potential, oligomycin, ATP synthase, electron transport chain
MeSH terms
Amino Acid Sequence, Cell Line, Cloning, Molecular, Dose-Response Relationship, Drug, Enzyme Inhibitors, Etoposide, Humans, Immunohistochemistry, Membrane Potentials, Microscopy, Fluorescence, Mitochondria, Molecular Sequence Data, Oligomycins, Protein Binding, RNA, Messenger, Rotenone, Thioredoxins, Time Factors, Tissue Distribution, Transfection, Blotting, Western, Cell Death, Sequence Homology, Amino Acid, DNA, Complementary, Mitochondrial Proteins, Mitochondrial Proton-Translocating ATPases

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