title: The roles of phosphate and the phosphate carrier in the mitochondrial permeability transition pore.
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.
authors.affiliation: School of Biochemistry and The Bristol Heart Institute, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Pinadda
authors.initials: P
authors.lastname: Varanyuwatana
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Halestrap
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D016572:Cyclosporine / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore; D028061:Phosphate Transport Proteins / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D028061:Phosphate Transport Proteins; D010710:Phosphates; D016572:Cyclosporine; D002118:Calcium