Electrophysiology clarifies the megariddles of the mitochondrial permeability transition pore

Abstract 

After a brief review of the early history of mitochondrial electrophysiology, the contribution of this approach to the study of the mitochondrial permeability transition (MPT) is recapitulated. It has for example provided evidence for a dimeric nature of the MPT pore, allowed the distinction between two levels of control of its activity, and underscored the relevance of redox events for the phenomenon. Single-channel recording provides a means to finally solve the riddle of the biochemical entity underlying it by comparing the characteristics of the pore with those of channels formed by candidate molecules or complexes. The possibility that this entity may be the protein import machinery of the inner mitochondrial membrane is emphasized.

Abbreviations: AAC2, ADP/ATP carrier 2, ANT, adenine nucleotide translocator, BHT, di-t-butylhydroxytoluene, CL, cardiolipin, CsA, cyclosporin A, CypD, cyclophilin D, Cx43, connexin-43, ΔΨ, mitochondrial transmembrane voltage gradient, HBSS, Hank’s balanced saline solution, HCT116, human colon tumor 116, Hepes, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, HP, Half-PTP, IMAC, inner membrane anion channel, IMM, inner mitochondrial membrane, MEF, mouse embryonic fibroblast, MCC, multi-conductance channel, MMC, mitochondrial megachannel, MPTP, mitocondrial permeability transition pore, OMM, outer mitochondrial membrane, PSC, peptide-sensitive channel, RLM, rat liver mitochondria, TSPO, translocator protein, VDAC, voltage dependent anion channel (mitochondrial porin), WT, wild-type

Keywords: Patch-clamp, Permeability transition pore, Mitochondrial megachannel, Electrophysiology, Mitochondrial protein import, Tim23