Ascorbate Peroxidase Acts As a Novel Determiner of Redox Homeostasis in Leishmania
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Ascorbate Peroxidase Acts As a Novel Determiner of Redox Homeostasis in Leishmania
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| Creator |
Adak, Subrata
Pal, Swati |
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| Subject |
Structural Biology & Bioinformatics
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| Description |
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. 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. 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. 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.
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| Date |
2012
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1664/1/ars.2012.pdf
Adak, Subrata and Pal, Swati (2012) Ascorbate Peroxidase Acts As a Novel Determiner of Redox Homeostasis in Leishmania. Antioxidants & Redox Signaling. |
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| Relation |
http://dx.doi.org/10.1089/ars.2012.4745
http://www.eprints.iicb.res.in/1664/ |
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