Oxidative modification of mitochondrial respiratory complexes in response to the stress of Trypanosoma cruzi infection.
Previously, we have shown deficiencies in the activities of the mitochondrial respiratory complexes and reduced mitochondrial ATP generation capacity in chagasic hearts infected by Trypanosoma cruzi. In this study, we determined whether the oxidative stress that occurs in response to T. cruzi infection contributes to the catalytic impairment of respiratory complexes and to subsequent mitochondrial dysfunction in murine myocardium. Our data show that oxidative injuries, as determined by the levels of lipid peroxides and protein carbonyls, are incurred in cardiac mitochondria as early as 3 days postinfection and persist throughout the infection and disease. The individual components of the respiratory complexes were separated by two-dimensional, blue-native gel electrophoresis, and carbonyl adducts were detected by Western blotting. We observed substantial carbonylation of the specific subunits of mitochondrial respiratory complexes in infected murine hearts. Of note is the oxidative modification of NDUFS1, NDUFS2, and NDUFV1, which form the catalytic core of the CI complex; UQCRC1, UQCRC2, and UQCRQ, the subunits of the core subcomplex, and UQCRH and CYC1, which form the cyt c(1) subcomplex of CIII; and a gamma chain that is essential for ATP synthesis by CV complex. The extent of oxidative modifications of the subunits correlated with the catalytic defects of the respiratory complexes in the infected myocardium. Taken together, our data demonstrate that respiratory complexes are oxidatively damaged in response to the stress of T. cruzi infection. These data also suggest involvement of the specific susceptibility of the protein subunits, and not generalized mitochondrial oxidative damage in respiratory chain impairment of chagasic hearts.
Wen
Jian-Jun
JJ
Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
Garg
Nisha
N
D000375:Aging / Q000502:physiology; D000818:Animals; D014355:Chagas Disease / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology*; D042967:Electron Transport Complex I / Q000378:metabolism*; D006321:Heart / Q000469:parasitology; D015227:Lipid Peroxidation; D008297:Male; D051379:Mice; D008929:Mitochondria, Heart / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D014349:Trypanosoma cruzi / Q000502:physiology*
D042967:Electron Transport Complex I; C000592113:NDUFV1 protein, mouse