Mitochondrial and bioenergetic dysfunction in human hepatic cells infected with dengue 2 virus.
Dengue virus infection affects millions of people all over the world. Although the clinical manifestations of dengue virus-induced diseases are known, the physiopathological mechanisms involved in deteriorating cellular function are not yet understood. In this study we evaluated for the first time the associations between dengue virus-induced cell death and mitochondrial function in HepG2, a human hepatoma cell line. Dengue virus infection promoted changes in mitochondrial bioenergetics, such as an increase in cellular respiration and a decrease in DeltaPsim. These alterations culminated in a 20% decrease in ATP content and a 15% decrease in the energy charge of virus-infected cells. Additionally, virus-infected cells showed several ultrastructural alterations, including mitochondria swelling and other morphological changes typical of the apoptotic process. The alterations in mitochondrial physiology and energy homeostasis preceded cell death. These results indicate that HepG2 cells infected with dengue virus are under metabolic stress and that mitochondrial dysfunction and alterations in cellular ATP balance may be related to the pathogenesis of dengue virus infection.
El-Bacha
Tatiana
T
Laboratório de Bioquímica de Vírus, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, RJ-Brazil. tatiana_elbacha@yahoo.com.br
Midlej
Victor
V
Pereira da Silva
Ana Paula
AP
Silva da Costa
Leandro
L
Benchimol
Marlene
M
Galina
Antonio
A
Da Poian
Andrea T
AT
D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D003715:Dengue / Q000378:metabolism* / Q000473:pathology; D003716:Dengue Virus / Q000378:metabolism*; D004734:Energy Metabolism; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology; D053078:Membrane Potential, Mitochondrial; D008930:Mitochondria, Liver / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology
D000255:Adenosine Triphosphate