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Kharechkina 2019 Biochim Biophys Acta Gen Subj
Additional label 2019-02  +
Coupling states LEAK  + , OXPHOS  + , ET  +
Has abstract The opening of the permeability transition
The opening of the permeability transition pore (PTP) in mitochondria plays a critical role in the pathogenesis of numerous diseases. Mitochondrial matrix pyridine nucleotides are potent regulators of the PTP, but the role of extramitochondrial nucleotides is unclear. The PTP opening was explored in isolated mitochondria and mitochondria in permeabilized differentiated and undifferentiated cells in the presence of added NAD(P)(H) in combination with Mg<sup>2+</sup>, adenine nucleotides (AN), and the inhibitors of AN translocase (ANT), voltage-dependent anion channel (VDAC), and cyclophilin D. Added NAD(H) and AN, but not NADP(H), inhibited the PTP opening with comparable potency. PTP suppression required neither NAD(H) oxidation nor reduction. The protective effects of NAD(H) and cyclosporin A were synergistic, and the effects of NAD(H) and millimolar AN were additive. The conformation-specific ANT inhibitors were unable to cancel the protective effect of NADH even under total ANT inhibition. Besides, NAD(H) activated the efflux of mitochondrial AN via ANT. VDAC ligand (Mg<sup>2+</sup>) and blockers (G3139 and 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid) potentiated and attenuated the protective effect of NAD(H), respectively. However, in embryonic and cancer (undifferentiated) cells, in contrast to isolated differentiated hepatocytes and cardiocytes, the suppression of PTP opening by NADH was negligible though all cells tested possessed a full set of VDAC isoforms. The study revealed a novel mechanism of PTP regulation by external (cytosolic) NAD(H) through the allosteric site in the OM or the intermembrane space. The mechanism might contribute to the resistance of differentiated cells under different pathological conditions including ischemia/reperfusion. <small>Copyright © 2019. Published by Elsevier B.V.</small>
. Published by Elsevier B.V.</small>  +
Has editor [[Plangger M]]  +
Has info [ PMID: 30763605]  +
Has publicationkeywords ATP  + , Differentiated cells  + , External site  + , NADH  + , Permeability transition pore  + , Poly(ADP-ribose) polymerase  +
Has title Kharechkina ES, Nikiforova AB, Teplova VV, Odinokova IV, Krestinina OV, Baburina YL, Kruglova SA, Kruglov AG (2019) Regulation of permeability transition pore opening in mitochondria by external NAD(H). Biochim Biophys Acta Gen Subj 1863:771-83.  +
Instrument and method Oxygraph-2k  +
Mammal and model Rat  +
MiP area Respiration  +
Pathways S  +
Preparation Isolated mitochondria  +
Respiration and regulation Calcium  + , Redox state  +
Stress Permeability transition  +
Tissue and cell Liver  +
Was published in journal Biochim Biophys Acta Gen Subj +
Was published in year 2019  +
Was written by Kharechkina ES + , Nikiforova AB + , Teplova VV + , Odinokova IV + , Krestinina OV + , Baburina YL + , Kruglova SA + , Kruglov AG +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
10:10:29, 26 July 2019  +
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