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
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1
Department of Medical Biochemistry, Semmelweis University, Hungary
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2
Buck Institute of Aging Research, United States
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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
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Received:
04 Mar 2009;
Published Online:
04 Mar 2009.
*
Correspondence:
Christos Chinopoulos, Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary, cchinopoulos@yahoo.com