The roles of phosphate and the phosphate carrier in the mitochondrial permeability transition pore |
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Authors: | Varanyuwatana Pinadda Halestrap Andrew P |
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Affiliation: | School of Biochemistry and The Bristol Heart Institute, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK. |
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Abstract: | Phosphate activation of the mitochondrial permeability transition pore (MPTP) opening is well-documented and could involve the phosphate carrier (PiC) that we have proposed is the pore's cyclophilin-D binding component. However, others have reported that following CyP-D ablation Pi inhibits MPTP opening while cyclosporine-A (CsA) inhibits MPTP opening only when Pi is present. Here we demonstrate that Pi activates MPTP opening under all energised and de-energised conditions tested while CsA inhibits pore opening whether or not Pi is present. Using siRNA in HeLa cells we could reduce PiC expression by 65-80% but this inhibited neither mitochondrial calcium accumulation nor MPTP opening. |
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