Leishmania infantum: provision of reducing equivalents to the mitochondrial tryparedoxin/tryparedoxin peroxidase system.
Within the mitochondrion of Leishmania infantum, hydroperoxide metabolism relies on the activity of tryparedoxin-dependent peroxidases (TXNPxs). Tryparedoxins (TXNs) are thioredoxin-related oxidoreductases, which in vitro are reduced by the trypanothione reductase/trypanothione [TR/T(SH)(2)] redox couple. Still, there is no evidence that this actually occurs in the mitochondrion. This communication addresses the question of how the mitochondrial TXN/TXNPx system is reduced. First, using a digitonin fractionation assay, we show that TR activity is absent from the L. infantum mitochondrion. The possibility that this organelle possesses alternative electron sources for TXN/TXNPx is then investigated. Biochemical assays performed with purified recombinant enzymes, revealed that TR and T(SH)(2) can be replaced, albeit less efficiently, by the dihydrolipoamide dehydrogenase/lipoamide redox system as TXN/TXNPx electron donor. This result challenges the classical view that T(SH)(2) is the only reductant for TXNs and add new prospects regarding the involvement of 2-oxo acid dehydrogenase complexes in L. infantum mitochondrial hydroperoxide metabolism.
Castro
Helena
H
IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
Romao
Susana
S
Gadelha
Fernanda R
FR
Tomás
Ana M
AM
D000818:Animals; D004072:Digitonin; D007202:Indicators and Reagents; D018314:Leishmania infantum / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D010545:Peroxides / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism*
D007202:Indicators and Reagents; D010545:Peroxides; D015800:Protozoan Proteins; C114110:tryparedoxin; D013879:Thioredoxins; D010544:Peroxidases; C110959:tryparedoxin peroxidase; D004072:Digitonin