Down-regulation of mitochondrial cytochrome c oxidase in senescent porcine pulmonary artery endothelial cells.
Cellular aging is associated with dysfunction of the mitochondrial respiration chain. Deficiency of mitochondrial cytochrome c oxidase (complex IV) plays a critical role in aging-induced mitochondrial dysfunction. We investigated whether in vitro cellular aging causes the downregulation of complex IV activity and gene expression using senescent (passage 45) and young (passage 3) pulmonary artery endothelial cells (PAEC). In senescent PAEC, the catalytic activity of complex IV decreased 84%, compared to that in young cells. Relative protein levels of complex IV subunits I and IV (complex IV S1 and S4) in senescent cells decreased 91%, compared to those in young cells. This suggests that lack of complex IV S1 and S4 in senescent cells may contribute to the deficiency of complex IV. Total steady state levels of mRNA for complex IV S1 and S4 in senescent cells were decreased to 20% and 18% of those in young cells. The relative rates of mRNA synthesis of complex IV S1 and S4 were decreased 46% and 37% in senescent cells, respectively, compared to young cells. The degradation of complex IV S1 and S4 was increased 76% and 64% in senescent cells, compared to young cells. These data indicate that mitochondrial DNA-encoded subunit I and nuclear DNA-encoded subunit IV of complex IV are downregulated through reduced synthesis and enhanced degradation of their mRNA, which may be responsible for the deficiency of complex IV in replicative senescent PAEC.
Zhang
Jianliang
J
Department of Medicine, University of Florida, Gainesville, FL 32608-1197, USA. zhangjl@medicine.ufl.edu
Block
Edward R
ER
Patel
Jawaharlal M
JM
D000818:Animals; D002384:Catalysis; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D015536:Down-Regulation; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D008928:Mitochondria / Q000201:enzymology*; D011651:Pulmonary Artery; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine
D012333:RNA, Messenger; D003576:Electron Transport Complex IV