616
Views
46
CrossRef citations to date
0
Altmetric
Original

Electrophysiological characterization of the Cyclophilin D-deleted mitochondrial permeability transition pore

, , &
Pages 521-530 | Received 27 Apr 2006, Published online: 09 Jul 2009
 

Abstract

Mitochondria isolated from engineered mice lacking Cyclophilin D (CypD), a component of the Permeability Transition Pore (PTP) complex, can still undergo a Ca2 + -dependent but Cyclosporin A-insensitive permeabilization of the inner membrane. Higher Ca2 +  concentrations are required than for wild-type controls. The characteristics of the pore formed in this system were not known, and it has been proposed that they might differ substantially from those of the normal PTP. To test this hypothesis, we have characterized the PTP of isogenic wild-type and CypD mouse liver mitochondria in patch clamp experiments, which allow biophysical characterization. The pores observed in the two cases, very similar to those of rat liver mitochondria, are indistinguishable according to a number of criteria. The only clear difference is in their sensitivity to Cyclosporin A. CypD is thus shown to be an auxiliary, modulatory component of the “standard” PTP, which forms and has essentially the same properties even in its absence. The observations suggest that Ca2 + , CypD, and presumably other inducers and inhibitors act at the level of an activation or assembly process. Activation is separate and upstream of the gating observable on a short or medium-term time scale. Once the pore is activated, its molecular dynamics and biophysical properties may thus be predicted not to depend on the details of the induction process.

Acronyms
ANT=

Adenine Nucleotide Translocator

CL=

Cardiolipin

CSA=

Cyclosporin A

CypD=

Cyclophilin D (mitochondrial cis-trans peptidyl-prolyl isomerase)

Erev=

current reversal potential

MLM=

Mouse Liver Mitochondria

MMC=

Mitochondrial MegaChannel

PT=

Permeability Transition

PTP=

Permeability Transition Pore

RLM=

Rat Liver Mitochondria

Ub0=

Ubiquinone 0

VDAC=

Voltage-Dependent Anion Channel (mitochondrial porin)

Acronyms
ANT=

Adenine Nucleotide Translocator

CL=

Cardiolipin

CSA=

Cyclosporin A

CypD=

Cyclophilin D (mitochondrial cis-trans peptidyl-prolyl isomerase)

Erev=

current reversal potential

MLM=

Mouse Liver Mitochondria

MMC=

Mitochondrial MegaChannel

PT=

Permeability Transition

PTP=

Permeability Transition Pore

RLM=

Rat Liver Mitochondria

Ub0=

Ubiquinone 0

VDAC=

Voltage-Dependent Anion Channel (mitochondrial porin)

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.