Elucidation of the effects of lipoperoxidation on the mitochondrial electron transport chain using yeast mitochondria with manipulated fatty acid content.
Lipoperoxidative damage to the respiratory chain proteins may account for disruption in mitochondrial electron transport chain (ETC) function and could lead to an augment in the production of reactive oxygen species (ROS). To test this hypothesis, we investigated the effects of lipoperoxidation on ETC function and cytochromes spectra of Saccharomyces cerevisiae mitochondria. We compared the effects of Fe(2+) treatment on mitochondria isolated from yeast with native (lipoperoxidation-resistant) and modified (lipoperoxidation-sensitive) fatty acid composition. Augmented sensitivity to oxidative stress was observed in the complex III-complex IV segment of the ETC. Lipoperoxidation did not alter the cytochromes content. Under lipoperoxidative conditions, cytochrome c reduction by succinate was almost totally eliminated by superoxide dismutase and stigmatellin. Our results suggest that lipoperoxidation impairs electron transfer mainly at cytochrome b in complex III, which leads to increased resistance to antimycin A and ROS generation due to an electron leak at the level of the Q(O) site of complex III.
Cortés-Rojo
Christian
C
Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Edificio B-3. CU, Morelia, Mich 58030, México.
Calderón-Cortés
Elizabeth
E
Clemente-Guerrero
Mónica
M
Estrada-Villagómez
Mirella
M
Manzo-Avalos
Salvador
S
Mejía-Zepeda
Ricardo
R
Boldogh
Istvan
I
Saavedra-Molina
Alfredo
A
D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology*; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism* / Q000502:physiology
D045222:Electron Transport Chain Complex Proteins; D005227:Fatty Acids; D017382:Reactive Oxygen Species; D007501:Iron