The roles of phosphate and the phosphate carrier in the mitochondrial permeability transition pore

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 MPT...

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Detalles Bibliográficos
Autores principales: Varanyuwatana, Pinadda, Halestrap, Andrew P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Science 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281194/
https://www.ncbi.nlm.nih.gov/pubmed/21586347
http://dx.doi.org/10.1016/j.mito.2011.04.006
Descripción
Sumario: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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