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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. Copyright © 2011 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Citation

Pinadda Varanyuwatana, Andrew P Halestrap. The roles of phosphate and the phosphate carrier in the mitochondrial permeability transition pore. Mitochondrion. 2012 Jan;12(1):120-5

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PMID: 21586347

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