Two linked genes of Leishmania infantum encode tryparedoxins localised to cytosol and mitochondrion

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Castro, H (Author) Other; Sousa, C (Author) Other; Novais, M (Author) Other; Santos, M (Author) Other; Budde, H (Author) Other; Cordeiro da Silva, A (Author) FFUP; Flohe, L (Author) Other; Tomaa, AM (Author) ICBAS

Journal

Title: Molecular and Biochemical Parasitology

Vol. 136

Pages: 137-147

ISSN: 0166-6851

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 48 Citations

Scopus - 57 Citations

Scientific classification

FOS: Medical and Health sciences > Health sciences

Other information

Authenticus ID: P-000-99B

DOI: 10.1016/j.molbiopara.2004.02.015

Abstract (EN): Tryparedoxins are components of the hydroperoxide detoxification cascades of Kinetoplastida, where they mediate electron transfer between trypanothione and a peroxiredoxin, which reduces hydroperoxides and possibly peroxynitrite. Tryparedoxins may also be involved in DNA synthesis, by their capacity to reduce ribonucleotide reductase. Here we report on the isolation of two tryparedoxin genes from Leishmania infantum, LiTXN1 and LiTXN2, which share the same genetic locus. These genes are both single copy and code for two active tryparedoxin enzymes, LiTXN1 and LiTXN2, with different biochemical and biological features. LiTXN1 is located to the cytosol and is upregulated in the infectious forms of the parasite, strongly suggesting that it might play an important role during infection. LiTXN2 is the first mitochondrial tryparedoxin described in Kinetoplastida. Biochemical assays performed on the purified recombinant proteins have shown that LiTXN1 preferentially reduces the cytosolic L. infantum peroxiredoxins, LicTXNPx1 and LicTXNPx2, whereas LiTXN2 has a higher specific activity for a mitochondrial peroxiredoxin, LimTXNPx. Kinetically, the two tryparedoxins follow a ping-pong mechanism and show no saturation. We suggest that LiTXN1 and LiTXN2 are part of two distinct antioxidant machineries, one cytosolic, the other mitochondrial, that complement each other to ensure effective defence from several sources of oxidants throughout the development of L. infantum.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11