On the role of the respiratory complex I on membrane permeability transition.
In this work we studied permeability transition by incubating mitochondria in the presence of 50 muM Ca(2+) and malate/glutamate as substrates. This condition, besides inducing the release of pyridine nucleotides, promotes the generation of reactive oxygen-derived species by the complex I of the respiratory chain. The latter leads to the opening of the mitochondrial permeability transition pore. Ca(2+) release, mitochondrial swelling and collapse of the transmembrane electric potential, were analyzed to assess this process. We propose that the mechanism for pore opening, in addition to the oxidative stress, involves the uncoupling effect of fatty acids providing activation of phospholipase A2, lipid peroxidation, and the oxidation of membrane thiols. This proposal emerges from the data indicating the protective effect of bovine serum albumin and N-ethylmaleimide. The key role of reactive oxygen species was implied based on the fact that the scavenger alpha-phenyl-tert-butyl nitrone inhibited pore opening.
García
Noemí
N
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, México, D.F., México 014080.
Correa
Francisco
F
Chávez
Edmundo
E
D000818:Animals; D042967:Electron Transport Complex I / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D007425:Intracellular Membranes / Q000502:physiology*; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008293:Malates / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010539:Permeability; D051381:Rats
D008293:Malates; D018698:Glutamic Acid; C030298:malic acid; D042967:Electron Transport Complex I