Thermodynamic Constraints in the Reversal of Adenine Nucleotide Translocase During the Reversal of F0-F1 ATP Synthase Caused by Respiratory Chain Inhibition: Critical Role of Substrate-Level Phosphorylation

Abstract

Event Abstract Back to Event Thermodynamic Constraints in the Reversal of Adenine Nucleotide Translocase During the Reversal of F0-F1 ATP Synthase Caused by Respiratory Chain Inhibition: Critical Role of Substrate-Level Phosphorylation Christos Chinopoulos1*, Miklos Mandi1, Katalin Mathe1, Akos A. Gerencser2, Beata Torocsik1, Judit Doczi1, Laszlo Csanady1, Lilla Turiak1, Szilvia Vajda1, Viktoria Vereczki3 and Vera Adam-Vizi1 1 Department of Medical Biochemistry, Semmelweis University, Hungary 2 Buck Institute of Aging Research, United States 3 Department of Anatomy, Semmelweis University, Hungary Mitochondria are the main ATP producers in the cell. However, conditions that bring the electron flow to a standstill and prevent proton pumping through the respiratory complexes convert mitochondria to ATP consumers. This is accomplished by the reversal of the F0-F1 ATP synthase antagonizing a collapse in membrane potential at the expense of ATP hydrolysis. The consensus is that under these conditions, extramitochondrial ATP producing pathways are strained to provide ATP to the mitochondrial matrix chiefly through the reversal of the ANT. Here we show that inhibition of the respiratory chain may shift the membrane potential to a range bracketed by the reversal potential of the F0-F1 ATPase and of the ANT, the latter being more negative than the former. As a consequence of this, reversal of the ATP synthase supported by matrical ATP pools generates a sufficient membrane potential to oppose the ANT from operating in reverse mode for as long as substrate-level phosphorylation is maintained. During respiratory chain inhibition the ANT can only reverse by a concomitant uncoupling in which the membrane potential attains values more positive than the reversal potential of the ANT, or by incapacitating substrate-level phosphorylation, a maneuver that shifts the reversal potential of the ANT towards more negative values than the prevailing membrane potential. It is suggested that in disease states encompassing respiratory chain inhibition in which mitochondria have not suffered yet a severe loss in membrane potential while still capable of substrate-level phosphorylation, these organelles may not contribute to cytosolic ATP depletion. Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Pathophysiology and neurology - degenerative disorders Citation: Chinopoulos C, Mandi M, Mathe K, Gerencser AA, Torocsik B, Doczi J, Csanady L, Turiak L, Vajda S, Vereczki V and Adam-Vizi V (2009). Thermodynamic Constraints in the Reversal of Adenine Nucleotide Translocase During the Reversal of F0-F1 ATP Synthase Caused by Respiratory Chain Inhibition: Critical Role of Substrate-Level Phosphorylation. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.141 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Mar 2009; Published Online: 04 Mar 2009. * Correspondence: Christos Chinopoulos, Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary, cchinopoulos@yahoo.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Christos Chinopoulos Miklos Mandi Katalin Mathe Akos A Gerencser Beata Torocsik Judit Doczi Laszlo Csanady Lilla Turiak Szilvia Vajda Viktoria Vereczki Vera Adam-Vizi Google Christos Chinopoulos Miklos Mandi Katalin Mathe Akos A Gerencser Beata Torocsik Judit Doczi Laszlo Csanady Lilla Turiak Szilvia Vajda Viktoria Vereczki Vera Adam-Vizi Google Scholar Christos Chinopoulos Miklos Mandi Katalin Mathe Akos A Gerencser Beata Torocsik Judit Doczi Laszlo Csanady Lilla Turiak Szilvia Vajda Viktoria Vereczki Vera Adam-Vizi PubMed Christos Chinopoulos Miklos Mandi Katalin Mathe Akos A Gerencser Beata Torocsik Judit Doczi Laszlo Csanady Lilla Turiak Szilvia Vajda Viktoria Vereczki Vera Adam-Vizi Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.