Plasmodium falciparum thioredoxin and glutathione-dependent redox proteins

Plasmodium falciparum relies on a network of enzymes for maintaining redox homeostasis, primarily involving the thioredoxin and glutathione systems—these include thioredoxin reductase (PfTrxR), glutathione reductase (PfGR), and associated redox proteins[3][7]. These proteins buffer cellular oxidative stress, detoxify reactive oxygen species, and provide reducing equivalents for essential metabolic and biosynthetic functions[3][6][7]. Peroxide-based antimalarials such as artemisinin and ozonides function partly by alkylating and disrupting these redox proteins, leading to parasite death[1][2][4]. The thioredoxin system is essential for P. falciparum survival, with knockout of thioredoxin reductase proving lethal[3][7]. These proteins are under investigation as therapeutic targets, with ongoing drug discovery efforts seeking selective inhibitors due to structural differences from human homologs[3][6].

Other names

Thioredoxin reductase (PfTrxR)Glutathione reductase (PfGR)Ferredoxin/Ferredoxin-NADP+ reductase system (Fd/FNR system)Redox homeostasis proteins

Alkylation and inhibition by peroxide antimalarials, leading to disrupted redox balance and parasite death[1][2][4]. Inhibition of thioredoxin reductase or glutathione reductase disrupts parasite antioxidant defense[3][6][7].