Journal of Biological Chemistry
Volume 277, Issue 36, 6 September 2002, Pages 33249-33257
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ENZYME CATALYSIS AND REGULATION
Human Mitochondrial Thioredoxin: INVOLVEMENT IN MITOCHONDRIAL MEMBRANE POTENTIAL AND CELL DEATH*

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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, ΔΨm. 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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Published, JBC Papers in Press, June 21, 2002, DOI 10.1074/jbc.M203036200

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This work was supported by grants from the Swedish Medical Research Council (Project 13X-10370 and 19X-11622-03C), the Karolinska Institutet, So¨derto¨rns Ho¨gskola, Swedish Medical Research Council (Projects 038-14096-01A, 03X-14041-01A), and Åke Wibergs stiftelse (to A .M -V.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EBI Data Bank with accession number(s) .