Premium
Oligomycin strengthens the effect of cyclosporin A on mitochondrial permeability transition by inducing phosphate uptake
Author(s) -
Chávez Edmundo,
Rodríguez José S.,
García Gerardo,
García Noemí,
Correa Francisco
Publication year - 2005
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2005.03.009
Subject(s) - oligomycin , mitochondrial permeability transition pore , phosphate , chemistry , permeability (electromagnetism) , biophysics , transition (genetics) , microbiology and biotechnology , biochemistry , biology , apoptosis , membrane , atpase , enzyme , programmed cell death , gene
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 Ca 2+ 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 Ca 2+ , 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 Ca 2+ . We concluded that oligomycin increases phosphate uptake by stimulating the phosphate − /OH − exchange reaction.