Regulation of the Permeability Transition Pore in Skeletal Muscle Mitochondria MODULATION BY ELECTRON FLOW THROUGH THE RESPIRATORY CHAIN COMPLEX I

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作者：

E Fontaine，O Eriksson，F Ichas，P Bernardi

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摘要：

We have investigated the regulation of the permeability transition pore (PTP), a cyclosporin A-sensitive channel, in rat skeletal muscle mitochondria. As is the case with mitochondria isolated from a variety of sources, skeletal muscle mitochondria can undergo a permeability transition following Ca2+ uptake in the presence of Pi. We find that the PTP opening is dramatically affected by the substrates used for energization, in that much lower Ca2+ loads are required when electrons are provided to complex I rather than to complex II or IV. This increased sensitivity of PTP opening does not depend on differences in membrane potential, matrix pH, Ca2+ uptake, oxidation-reduction status of pyridine nucleotides, or production of H2O2, but is directly related to the rate of electron flow through complex I. Indeed, and with complex I substrates only, pore opening can be observed when depolarization is induced with uncoupler (increased electron flow) but not with cyanide (decreased electron flow). Consistent with pore regulation by electron flow, we find that PTP opening is inhibited by ubiquinone 0 at concentrations that partially inhibit respiration and do not depolarize the inner membrane. These data allow identification of a novel site of regulation of the PTP, suggest that complex I may be part of the pore complex, and open new perspectives for its pharmacological modulation in living cells.

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关键词：

socketed pile in soft rock red beds side resistance of rock-socketed pile

DOI：

10.1074/jbc.273.20.12662

被引量：

751

年份：

1998