Physiological effectors modify voltage sensing by the cyclosporin A-sensitive permeability transition pore of mitochondria
This paper reports an investigation on the modulation of the mitochondrial permeability transition pore (MTP) by the membrane potential. Energized rat liver mitochondria loaded with a small Ca2+ pulse in sucrose medium supplemented with phosphate favor a high MTP "closed" probability becau...
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Published in: | The Journal of biological chemistry 1993-10, Vol.268 (29), p.21939-21945 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | This paper reports an investigation on the modulation of the mitochondrial permeability transition pore (MTP) by the membrane
potential. Energized rat liver mitochondria loaded with a small Ca2+ pulse in sucrose medium supplemented with phosphate favor
a high MTP "closed" probability because of the high membrane potential and therefore maintain a low permeability to sucrose.
Upon depolarization by the addition of fully uncoupling concentrations of carbonyl cyanide p-trifluoromethoxyphenylhydrazone
(FCCP) mitochondria favor a high MTP "open" probability and rapidly undergo a process of osmotic swelling following sucrose
diffusion toward the matrix. A titration with FCCP reveals that discrete subpopulations of mitochondria with different gating
potentials for MTP opening may exist, since increasing concentrations of FCCP increase the fraction of mitochondria undergoing
osmotic swelling. We show that physiological effectors (Ca2+, Mg2+, ADP, palmitate) modify pore opening in a mitochondrial
population by shifting the fraction of mitochondria with a functionally open pore at any given membrane potential. Many inducers
and inhibitors may therefore affect the pore directly through an effect on the MTP voltage sensing rather than indirectly
through an effect on the membrane potential. Thus, many effectors may induce pore opening by shifting the MTP gating potential
to higher levels, whereas many inhibitors may induce pore closure by shifting the MTP gating potential to lower levels. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/s0021-9258(20)80631-0 |