Ascorbate peroxidase acts as a novel determiner of redox homeostasis in Leishmania.
CONCLUSIONS
Reactive oxygen species (ROS) are produced as natural byproducts of metabolism and respiration. While physiological levels of ROS are required for vital cellular functions (e.g., development and proliferation), a living organism is faced with constant challenges due to accumulation or overproduction of ROS throughout its life. The life cycle of Leishmania parasite has led it to confront the highly oxidizing environment in the macrophage phagosomes, necessitating ROS homeostasis and signaling as key strategies for successful survival and pathogenicity.


BACKGROUND
Ascorbate peroxidase from Leishmania major (LmAPX) is the only heme peroxidase identified so far in Leishmania. Structural analysis and functional characterization of LmAPX have yielded interesting and novel insight on this enzyme. The protein has been found to be a hybrid of cytochrome c peroxidase and ascorbate peroxidase. This enzyme is colocalized with cytochrome c in the inner mitochondrial membrane facing the intermembrane space and shows higher activity toward cytochrome c oxidation.


RESULTS
Overexpression of LmAPX in L. major cells confers tolerance to oxidative stress-mediated cardiolipin oxidation and consequently protects cells from extensive protein damage. LmAPX-/- mutants show higher intracellular hydrogen peroxide (H₂O₂), which might signal for cellular transformation from noninfective procyclic to infective metacyclic form and ultimately apoptosis.


CONCLUSIONS
Manipulation of LmAPX expression has significantly added to the present understanding of the parasite's defense network against oxidative damage caused by H₂O₂. The future investigations will address more exactly the signaling pathways involved in redox homeostasis.
Division of Structural Biology and Bio-informatics, CSIR-Indian Institute of Chemical Biology, Kolkata, India. adaks@iicb.res.in
Subrata
S
Adak
Swati
S
Pal
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D060387:Ascorbate Peroxidases / Q000737:chemistry / Q000502:physiology*; D001205:Ascorbic Acid / Q000378:metabolism; D020134:Catalytic Domain; D006706:Homeostasis; D006801:Humans; D007891:Leishmania / Q000201:enzymology* / Q000276:immunology; D007896:Leishmaniasis / Q000276:immunology / Q000469:parasitology; D008958:Models, Molecular; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015800:Protozoan Proteins / Q000737:chemistry / Q000502:physiology*
D000975:Antioxidants; D015800:Protozoan Proteins; D060387:Ascorbate Peroxidases; D001205:Ascorbic Acid