MPTP opening differently affects electron transport chain and oxidative phosphorylation at succinate and NAD-dependent substrates oxidation in permeabilized rat hepatocytes

H M Mazur,B O Manko,V M Merlavsky,V V Manko,Ivan Franko National University Of Lviv, Ukraine

doi:10.15407/ubj92.04.014

Abstract

mPTP opening differently affects electron transport chain and oxidative phosphorylation at succinate and NAD-dependent substrates oxidation in permeabilized rat hepatocytes

Highlights

Concentration in the mitochondrial matrix increases the activity of pyruvate, isocitrate, α-ketoglutarate dehydrogenases and ATP synthesis [1]
While physiological role of transient pore activation is still not clear [4], the prolonged Ca2+-induced mitochondrial permeability transition pore (mPTP) opening leads to the respiration and oxidative phosphorylation uncoupling, ATP depletion and mitochondrial matrix swelling, cytochrome c release and apoptotic cells death [5,6,7,8]
We used Cyclosporin A (CsA) to test its effects of Ca2+-induced mPTP activation on respiration of digitonin-permeabilized hepatocytes

Summary

Introduction

Concentration in the mitochondrial matrix increases the activity of pyruvate, isocitrate, α-ketoglutarate dehydrogenases and ATP synthesis [1]. We used CsA to test its effects of Ca2+-induced mPTP activation on respiration of digitonin-permeabilized hepatocytes. Hepatocytes were added during the first series of experiments into a polarographic chamber where oxidation substrates – succinate (5 mM) or a mixture of malate, glutamate and pyruvate (5 mM) were present already at different Ca2+ concentrations.

Objectives

Results

Conclusion