Mitochondrial matrix pH controls oxidative phosphorylation and metabolism-secretion coupling in INS-1E clonal beta cells

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Dmitry AkhmedovAndreas Wiederkehr

Abstract

Glucose-evoked mitochondrial signals augment ATP synthesis in the pancreatic β cell. This activation of energy metabolism increases the cytosolic ATP/ADP ratio, which stimulates plasma membrane electrical activity and insulin granule exocytosis. We have recently demonstrated that matrix pH increases during nutrient stimulation of the pancreatic β cell. Here, we have tested whether mitochondrial matrix pH controls oxidative phosphorylation and metabolism-secretion coupling in the rat β-cell line INS-1E. Acidification of the mitochondrial matrix pH by nigericin blunted nutrient-dependent respiratory and ATP responses (continuously monitored in intact cells). Using electrophysiology and single cell imaging, we find that the associated defects in energy metabolism suppress glucose-stimulated plasma membrane electrical activity and cytosolic calcium transients. The same parameters were unaffected after direct stimulation of electrical activity with tolbutamide, which bypasses mitochondrial function. Furthermore, lowered matrix pH strongly inhibited sustained, but not first-phase, insulin secretion. Our results demonstrate that the matrix pH exerts a control function on oxidative phosphorylation in intact cells and that this mode of ...Continue Reading

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Apr 25, 2012·Pflügers Archiv : European journal of physiology·Damon Poburko, Nicolas Demaurex
May 30, 2012·The Journal of General Physiology·Jaime Santo-Domingo, Nicolas Demaurex
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Jul 26, 2011·Molecular and Cellular Endocrinology·Andreas Wiederkehr, Claes B Wollheim

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