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Eukaryotic Cell, May 2006, p. 861-870, Vol. 5, No. 5
1535-9778/06/$08.00+0     doi:10.1128/EC.5.5.861-870.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Expression of a Mitochondrial Peroxiredoxin Prevents Programmed Cell Death in Leishmania donovani{dagger}

Simone Harder,1 Meike Bente,1 Kerstin Isermann,2 and Iris Bruchhaus1*

Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany,1 Zoological Institute of the University of Kiel, Kiel, Germany2

Received 21 December 2005/ Accepted 19 January 2006

Leishmania promastigote cells transmitted by the insect vector get phagocytosed by macrophages and convert into the amastigote form. During development and transformation, the parasites are exposed to various concentrations of reactive oxygen species, which can induce programmed cell death (PCD). We show that a mitochondrial peroxiredoxin (LdmPrx) protects Leishmania donovani from PCD. Whereas this peroxiredoxin is restricted to the kinetoplast area in promastigotes, it covers the entire mitochondrion in amastigotes, accompanied by dramatically increased expression. A similar change in the expression pattern was observed during the growth of Leishmania from the early to the late logarithmic phase. Recombinant LdmPrx shows typical peroxiredoxin-like enzyme activity. It is able to detoxify organic and inorganic peroxides and prevents DNA from hydroxyl radical-induced damage. Most notably, Leishmania parasites overexpressing this peroxiredoxin are protected from hydrogen peroxide-induced PCD. This protection is also seen in promastigotes grown to the late logarithmic phase, also characterized by high expression of this peroxiredoxin. Apparently, the physiological role of this peroxiredoxin is stabilization of the mitochondrial membrane potential and, as a consequence, inhibition of PCD through removal of peroxides.


* Corresponding author. Mailing address: Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, 20359 Hamburg, Germany. Phone: (49) 4042818472. Fax: (49) 4042818512. E-mail: bruchhaus{at}bni-hamburg.de.

{dagger} Supplemental material for this article may be found at http://ec.asm.org/.


Eukaryotic Cell, May 2006, p. 861-870, Vol. 5, No. 5
1535-9778/06/$08.00+0     doi:10.1128/EC.5.5.861-870.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.







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Copyright © 2006 by the American Society for Microbiology.