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Malarial Infection Develops Mitochondrial Pathology and Mitochondrial Oxidative Stress to Promote Hepatocyte Apoptosis.

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Title Malarial Infection Develops Mitochondrial Pathology and Mitochondrial Oxidative Stress to Promote Hepatocyte Apoptosis.
 
Creator Dey, Sumanta
Guha, Mithu
Alam, Athar
Goyal, Manish
Bindu, Samik
Pal, Chinmay
Maity, Pallab
Mitra, Kalyan
Bandyopadhyay, Uday
 
Subject Infectious Diseases and Immunology
 
Description Activation of the mitochondrial apoptosis pathway by oxidative stress has been implicated in hepatocyte
apoptosis during malaria. Because mitochondria are the source and target of reactive oxygen species (ROS),
we have investigated whether hepatocyte apoptosis is linked to mitochondrial pathology and mitochondrial
ROS generation during malaria. Malarial infection induces mitochondrial pathology by inhibiting
mitochondrial respiration, dehydrogenases, and transmembrane potential and damaging the ultrastructure
as evident from transmission electron microscopic studies. Mitochondrial GSH depletion and formation of
protein carbonyl indicate that mitochondrial pathology is associated with mitochondrial oxidative stress.
Fluorescence imaging of hepatocytes documents intramitochondrial superoxide anion (O2
U−) generation
during malaria. O2
U− inactivates mitochondrial aconitase to release iron from iron–sulfur clusters, which
forms the hydroxyl radical (UOH) interacting with H2O2 produced concurrently. Malarial infection inactivates
mitochondrial aconitase, and carbonylation of aconitase is evident from Western immunoblotting. The
release of iron has been documented by fluorescence imaging of hepatocytes using Phen Green SK, and
mitochondrial UOH generation has been confirmed. During malaria, the depletion of cardiolipin and
formation of the mitochondrial permeability transition pore favor cytochrome c release to activate caspase-9.
Interestingly, mitochondrial UOH generation correlates with the activation of both caspase-9 and caspase-3
with the progress of malarial infection, indicating the critical role of UOH.
 
Publisher Elsevier
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1364/1/FREE_RADICAL_BIOLOGY_AND_MEDICINE___46_(_2)_271%2D281;2009[118].pdf
Dey, Sumanta and Guha, Mithu and Alam, Athar and Goyal, Manish and Bindu, Samik and Pal, Chinmay and Maity, Pallab and Mitra, Kalyan and Bandyopadhyay, Uday (2009) Malarial Infection Develops Mitochondrial Pathology and Mitochondrial Oxidative Stress to Promote Hepatocyte Apoptosis. Free Radical Biology & Medicine, 46 (2). pp. 271-281.
 
Relation http://dx.doi.org/10.1016/j.freeradbiomed.2008.10.032
http://www.eprints.iicb.res.in/1364/