ElBacha 2010 Abstract IOC60

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El-Bacha T, Abud M, Galina A, Da Poian AT (2010) Bioenergetics of liver mitochondria from mice infected with Dengue virus. MiPNet15.10.

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El-Bacha T, Abud M, Galina A, Da Poian AT (2010)

Event: MiPNet15.10_IOC60

DenV infection is the major worldwide life-threatening human arbovirosis. In Brazil, over 150,000 cases were notified this year, corresponding to a 70% increase compared to the same period in 2009. Hemostatic alterations and plasma leakage are some of events related to DenV pathogenesis, suggesting that microvascular endothelium function and integrity might have a primordial role in DenV diseases. Additionally, liver dysfunction plays a central role in severe infection. We have shown that DenV infection of human hepatic cells caused profound alterations on mitochondrial function, reflected by decreased mitochondrial membrane potential, efficiency in synthesizing ATP and intracellular ATP content (doi:10.1016/j.bbadis.2007.08.003). Few experimental models are recently been developed which reproduce many of the infection symptoms in humans. The aim of the present work was to evaluate the bioenergetics of isolated liver mitochondria from mice infected with DenV virus. 5-week old mice were infected or mock- infected with DenV virus (100 pfu/animal). After 5 days, animals were sacrificed for hematological analysis and liver mitochondria were isolated as described in MiPNet11.05. Liver mitochondria from DenV-infected animals presented altered bioenergetic parameters when compared to mitochondria from mock-infected animals. Oligomycin-sensitive respiration (coupled respiration) presented a 34% decrease in mitochondria from infected animals and when it was normalized by maximum Electron Transport System (ET-pathway) capacity (induced by FCCP) corresponded to 35% and 21% in mock and DenV-infected animals, respectively. Leak (oligomycin-insensitive) respiration was 17% increase in DenV-infected mitochondria, although no difference was detected when normalized by ET capacity, corresponding to 23 and 22% of maximum respiration in mock-infected and DenV-infected animals, respectively. Analyzing respiratory complexes-driven respiration it was found an increase in both respiratory control ratio of complex I and complex II in mitochondria from DenV-infected animals when compared to controls. These early alterations in mitochondrial bioenergetics in liver from infected mice might be associated to liver dysfunction characteristic of severe DenV infection. Particularly, alterations in oxygen consumption coupled to ATP synthesis might be related to the mechanisms by which DenV virus interact with mammalian host metabolism, manipulating and driving metabolic intermediates for their own replication. A detailed characterization of these alterations appears to be critical for the understanding of DenV pathogenesis and for the development of effective therapy against DenV diseases.


O2k-Network Lab: BR Rio de Janeiro Galina A, BR Rio de Janeiro Da Poian AT


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Organism: Mouse  Tissue;cell: Liver  Preparation: Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase 

Coupling state: OXPHOS 

HRR: Oxygraph-2k