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Ascorbate peroxidase acts as a novel determiner of redox homeostasis in Leishmania.
- Source :
-
Antioxidants & redox signaling [Antioxid Redox Signal] 2013 Sep 01; Vol. 19 (7), pp. 746-54. Date of Electronic Publication: 2012 Aug 02. - Publication Year :
- 2013
-
Abstract
- Significance: 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.<br />Recent Advances: 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.<br />Critical Issues: 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.<br />Future Directions: 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.
- Subjects :
- Animals
Antioxidants metabolism
Ascorbate Peroxidases chemistry
Ascorbic Acid metabolism
Catalytic Domain
Homeostasis
Humans
Leishmania immunology
Leishmaniasis immunology
Leishmaniasis parasitology
Models, Molecular
Oxidation-Reduction
Oxidative Stress
Protozoan Proteins chemistry
Ascorbate Peroxidases physiology
Leishmania enzymology
Protozoan Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1557-7716
- Volume :
- 19
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Antioxidants & redox signaling
- Publication Type :
- Academic Journal
- Accession number :
- 22703594
- Full Text :
- https://doi.org/10.1089/ars.2012.4745