Structural mechanisms of cyclophilin D-dependent control of the mitochondrial permeability transition pore
M Gutiérrez-Aguilar, CP Baines - Biochimica et Biophysica Acta (BBA) …, 2015 - Elsevier
M Gutiérrez-Aguilar, CP Baines
Biochimica et Biophysica Acta (BBA)-General Subjects, 2015•ElsevierBackground Opening of the mitochondrial permeability transition pore is the underlying
cause of cellular dysfunction during diverse pathological situations. Although this
bioenergetic entity has been studied extensively, its molecular componentry is constantly
debated. Cyclophilin D is the only universally accepted modulator of this channel and its
selective ligands have been proposed as therapeutic agents with the potential to regulate
pore opening during disease. Scope of review This review aims to recapitulate known …
cause of cellular dysfunction during diverse pathological situations. Although this
bioenergetic entity has been studied extensively, its molecular componentry is constantly
debated. Cyclophilin D is the only universally accepted modulator of this channel and its
selective ligands have been proposed as therapeutic agents with the potential to regulate
pore opening during disease. Scope of review This review aims to recapitulate known …
Background
Opening of the mitochondrial permeability transition pore is the underlying cause of cellular dysfunction during diverse pathological situations. Although this bioenergetic entity has been studied extensively, its molecular componentry is constantly debated. Cyclophilin D is the only universally accepted modulator of this channel and its selective ligands have been proposed as therapeutic agents with the potential to regulate pore opening during disease.
Scope of review
This review aims to recapitulate known molecular determinants necessary for Cyclophilin D activity regulation and binding to proposed pore constituents thereby regulating the mitochondrial permeability transition pore.
Major conclusions
While the main target of Cyclophilin D is still a matter of further research, permeability transition is finely regulated by post-translational modifications of this isomerase and its catalytic activity facilitates pore opening.
General significance
Complete elucidation of the molecular determinants required for Cyclophilin D-mediated control of the mitochondrial permeability transition pore will allow the rational design of therapies aiming to control disease phenotypes associated with the occurrence of this unselective channel. This article is part of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts and Drug Targets.
Elsevier