Oligomycin strengthens the effect of cyclosporin A on mitochondrial permeability transition by inducing phosphate uptake |
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Authors: | Chávez Edmundo Rodríguez José S García Gerardo García Noemí Correa Francisco |
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Institution: | Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, México, D.F. 014080, México. echavez@mail.ssa.gob.mx |
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Abstract: | The purpose of this work was to assess the effect of oligomycin on the mitochondrial membrane permeability transition. The antibiotic was found to strengthen cyclosporin A (CSA)-induced protection of non-specific permeability, which is triggered by a matrix Ca2+ load in the absence of ADP. Oligomycin also reinforced the protective effect of CSA on carboxyatractyloside-induced pore opening in the absence of ADP, but failed to do so in mitochondria incubated under anaerobic conditions or after addition of CCCP. Analyzing the efflux of matrix Ca2+, we found that mitochondrial swelling and the collapse of the transmembrane electric gradient coincided with membrane leakage. The effects of the antibiotic were observed in phosphate-containing media but not in the presence of acetate. Furthermore, N-ethylmaleimide hindered the protective effect of oligomycin-CSA. In addition, the matrix phosphate concentration increased concurrently with a diminution in the matrix-free fraction of Ca2+. We concluded that oligomycin increases phosphate uptake by stimulating the phosphate-/OH- exchange reaction. |
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Keywords: | Mitochondria Oligomycin Permeability transition Calcium Cyclosporin A Kidney |
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