Specificity and efficiency of thioredoxin action upon the 2-oxoacid dehydrogenase complexes are studied by using a number of thioredoxins and complexes. Bacterial and mammalian pyruvate and 2-oxoglutarate dehydrogenase systems display similar row of preference to thioredoxins that may result from thioredoxin binding to the homologous or common dihydrolipoamide dehydrogenase components of the complexes. The most sensitive to thioredoxin is the complex whose component exhibits the highest sequence similarity to eukaryotic thioredoxin reductase. Hence, thioredoxin binding to the complexes may be related to that in the thioredoxin reductase, a dihydrolipoamide dehydrogenase homolog. The highest potency of mitochondrial thioredoxin to affect the mitochondrial complexes is revealed. A 96-100% conservation of the mitochondrial thioredoxin structure is shown within the four known sequences and the N-terminus of the pig heart protein determined. Eleven thioredoxins tested biochemically are analyzed by multiple sequence alignment and homology modeling. Their effects correlate with the residues at the contact between the alpha 3/3(10) and alpha 1 helices, the length of the al helix and charges in the alpha 2-beta 3 and beta 4-beta 5 linkers. Polarization of the thioredoxin molecule and its active site surroundings are characterized. Thioredoxins with a highly polarized surface around the essential disulfide bridge (mitochondrial, pea f, and Arabidopsis thaliana h3) show low crossreactivity as compared to the species with a decreased polarization of this area (e.g., from Escherichia coli). The strongest polarization of the whole molecule results in the highest magnitude of the electrostatic dipole vector of mitochondrial thioredoxin. Thioredoxins with the dipole orientation similar to that of the latter have the affinities for the 2-oxoacid dehydrogenase complexes, proportional to the dipole magnitudes. Thioredoxin with an opposite dipole orientation shows no effect. Activating and inhibitory thioredoxin disulfides are distinguished by the charges of the residues 13/14 (alpha 1 helix), 51 (alpha 2-beta 3 linker), and 83/85 (beta 4-beta 5 linker), changing the dipole direction. The results show that the thioredoxin-target interplay may be controlled by the long-range interactions between the electrostatic dipole vectors of the proteins and the degree of their interface polarization.