The malarial parasite Plasmodium falciparum imports the human protein peroxiredoxin 2 for peroxide detoxification.
Coevolution of the malarial parasite and its human host has resulted in a complex network of interactions contributing to the homeodynamics of the host-parasite unit. As a rapidly growing and multiplying organism, Plasmodium falciparum depends on an adequate antioxidant defense system that is efficient despite the absence of genuine catalase and glutathione peroxidase. Using different experimental approaches, we demonstrate that P. falciparum imports the human redox-active protein peroxiredoxin 2 (hPrx-2, hTPx1) into its cytosol. As shown by confocal microscopy and immunogold electron microscopy, hPrx-2 is also present in the Maurer's clefts, organelles that are described as being involved in parasite protein export. Enzyme kinetic analyses prove that hPrx-2 accepts Plasmodium cytosolic thioredoxin 1 as a reducing substrate. hPrx-2 accounts for roughly 50% of thioredoxin peroxidase activity in parasite extracts, thus indicating a functional role of hPrx-2 as an enzymatic scavenger of peroxides in the parasite. Under chloroquine treatment, a drug promoting oxidative stress, the abundance of hPrx-2 in the parasite increases significantly. P. falciparum has adapted to adopt the hPrx-2, thereby using the host protein for its own purposes.
Koncarevic
Sasa
S
Interdisciplinary Research Center, Heinrich-Buff-Ring 26-32, D-35392 Giessen, Germany.
Rohrbach
Petra
P
Deponte
Marcel
M
Krohne
Georg
G
Prieto
Judith Helena
JH
Yates
John
J
Rahlfs
Stefan
S
Becker
Katja
K
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002457:Cell Extracts; D002738:Chloroquine / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000648:ultrastructure; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000469:parasitology / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D007700:Kinetics; D016778:Malaria, Falciparum / Q000469:parasitology*; D008565:Membrane Proteins / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism*; D054464:Peroxiredoxins / Q000378:metabolism* / Q000648:ultrastructure; D010963:Plasmodium falciparum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000187:drug effects; D015800:Protozoan Proteins / Q000378:metabolism; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
D002352:Carrier Proteins; D002457:Cell Extracts; D006454:Hemoglobins; D008565:Membrane Proteins; D010545:Peroxides; C417763:Pfsbp1 protein, Plasmodium falciparum; D015800:Protozoan Proteins; D049452:Green Fluorescent Proteins; D002738:Chloroquine; C086065:PRDX2 protein, human; D054464:Peroxiredoxins