title: Matrix alkalinisation unleashes β-cell mitochondria.
abstract: Recently, we have identified matrix pH as a key regulator of mitochondrial energy metabolism in the β-cell (Wiederkehr et al. EMBO J. (2009) 28(4):417-28). Under resting glucose conditions matrix pH in β-cell mitochondria is unusually low (pH 7.25). Following nutrient stimulation of rat islets matrix alkalinisation occurs raising matrix pH to 7.7 a value close to those determined in other cell types (pH 7.8-8.1). Alkalinisation follows a very similar time-course as net increases of the cytosolic ATP levels and is associated with a 2.5-fold elevation of the mitochondrial ATP synthesis rate. Suppression of this alkalinisation using nigericin almost completely abolishes mitochondrial ATP synthesis in a permeabilised cell system. Our working hypothesis is that low mitochondrial pH maintains the β-cell mitochondria in an inactive state, whereas nutrient stimulation favors alkalinisation and full activation of mitochondrial energy metabolism, resulting in mitochondrial signal generation and insulin granule exocytosis.
authors.affiliation: Department of Cell Physiology and Metabolism, University Medical Center, Geneva Switzerland. andreas.wiederkehr@unige.ch
authors.forename: Andreas
authors.initials: A
authors.lastname: Wiederkehr
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism* / Q000502:physiology; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D050417:Insulin-Secreting Cells / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology* / Q000648:ultrastructure; D019169:Jurkat Cells; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D051381:Rats
chemical_list: D000255:Adenosine Triphosphate