Mechanism of Dihydrolipoate Stimulation of the Mitochondrial Permeability Transition: Effect of Different Respiratory Substrates

The stimulation of the mitochondrial permeability transition (MPT) by dihydrolipoate (DHLA) was studied in rat liver mitochondria in the presence of different respiratory substrates. The Ca2+ threshold for the induction of MPT was lowest for pyruvate, followed by 2‐hydroxybutyrate, 2‐oxoglutarate, g...

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Bibliographic Details
Published in:IUBMB life 2000-03, Vol.49 (3), p.211-216
Main Authors: Morkunaite, Sarune, Teplova, Vera V., Saris, Nils‐Erik L.
Format: Article
Language:English
Subjects:
Dihydrolipoate
Glutathione
Mitochondria
Nucleotides
Oxygen
Permeability
Pyridine
Reactive
Species
Transition
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Summary:The stimulation of the mitochondrial permeability transition (MPT) by dihydrolipoate (DHLA) was studied in rat liver mitochondria in the presence of different respiratory substrates. The Ca2+ threshold for the induction of MPT was lowest for pyruvate, followed by 2‐hydroxybutyrate, 2‐oxoglutarate, glutamate plus malate, and succinate plus rotenone, both in the presence and absence of DHLA. DHLA was not able to induce MPT in the absence of Ca2+, in the presence of cyclosporin A, or rotenone with pyridine nucleotide‐dependent substrates. The difference in sensitivity of MPT to DHLA with various substrates was correlated with the redox state of pyridine nucleotides but not the redox state of glutathione. These findings demonstrate that DHLA induced MPT pore opening through the P‐site thiol. The similarities between the effect of DHLA and that of production of reactive oxygen species found in model experiments suggest that DHLA stimulates MPT by production of reactive oxygen species that exhaust the antioxidant defence.
ISSN:1521-6543
1521-6551
DOI:10.1080/713803622