Stronger control of ATP/ADP by proton leak in pancreatic beta-cells than skeletal muscle mitochondria.

TitleStronger control of ATP/ADP by proton leak in pancreatic beta-cells than skeletal muscle mitochondria.
Publication TypeJournal Article
Year of Publication2006
AuthorsAffourtit, C, Brand, MD
JournalBiochem J
Volume393
IssuePt 1
Pagination151-9
Date Published2006 Jan 01
ISSN1470-8728
KeywordsAdenosine Diphosphate, Adenosine Triphosphate, Animals, Cell Membrane, Female, Insulin-Secreting Cells, Membrane Potentials, Mitochondria, Muscle, Skeletal, Oxygen Consumption, Protons, Rats, Rats, Wistar
Abstract

Pancreatic beta cells respond to rising blood glucose concentrations by increasing their oxidative metabolism, which leads to an increased ATP/ADP ratio, closure of K(ATP) channels, depolarization of the plasma membrane potential, influx of calcium and the eventual secretion of insulin. Such a signalling mechanism implies that the ATP/ADP ratio is flexible in beta cells (beta-cells), which is in contrast with other cell types (e.g. muscle and liver) that maintain a stable ATP/ADP poise while respiring at widely varying rates. To determine whether this difference in flexibility is accounted for by mitochondrial peculiarities, we performed a top-down metabolic control analysis to quantitatively assess how ATP/ADP is controlled in mitochondria isolated from rat skeletal muscle and cultured beta cells. We show that the ATP/ADP ratio is more strongly controlled (approx. 7.5-fold) by proton leak in beta cells than in muscle. The comparatively high importance of proton leak in beta cell mitochondria (relative to phosphorylation) is evidenced furthermore by its relatively high level of control over membrane potential and overall respiratory activity. Modular-kinetic analysis of oxidative phosphorylation reveals that these control differences can be fully explained by a higher relative leak activity in beta cell mitochondria, which results in a comparatively high contribution of proton leak to the overall respiratory activity in this system.

DOI10.1042/BJ20051280
Alternate JournalBiochem. J.
Citation Key10.1042/BJ20051280
PubMed ID16137248
PubMed Central IDPMC1383673
Grant ListMC_U105663137 / / Medical Research Council / United Kingdom