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

被引:43
作者
De Marchi, Umberto
Basso, Emy
Szabo, Ildiko
Zoratti, Mario
机构
[1] CNR, Inst Neurosci, Dept Expt Biomed Sci, I-35121 Padua, Italy
[2] Univ Padua, Dept Biol, Padua, Italy
[3] Univ Padua, Dept Expt Biomed Sci, Padua, Italy
关键词
Cyclophilin D; permeability transition; mitochondria; channels; patch-clamp;
D O I
10.1080/09687860600907644
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:521 / 530
页数:10
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