Human mitochondrial thioredoxin. Involvement in mitochondrial membrane potential and cell death.
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.
Damdimopoulos
Anastasios E
AE
Department of Biosciences at Novum, Karolinska Institute, S-141 57 Huddinge, Sweden.
Miranda-Vizuete
Antonio
A
Pelto-Huikko
Markku
M
Gustafsson
Jan-Ake
JA
Spyrou
Giannis
G
D000595:Amino Acid Sequence; D015153:Blotting, Western; D016923:Cell Death; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D008969:Molecular Sequence Data; D009840:Oligomycins / Q000494:pharmacology; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection
D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D024101:Mitochondrial Proteins; D009840:Oligomycins; D012333:RNA, Messenger; C467002:TXN2 protein, human; D012402:Rotenone; D013879:Thioredoxins; D005047:Etoposide; D025261:Mitochondrial Proton-Translocating ATPases