High membrane potential promotes alkenal-induced mitochondrial uncoupling and influences adenine nucleotide translocase conformation.

The Biochemical Journal
Vian AzzuM D Brand

Abstract

Mitochondria generate reactive oxygen species, whose downstream lipid peroxidation products, such as 4-hydroxynonenal, induce uncoupling of oxidative phosphorylation by increasing proton leak through mitochondrial inner membrane proteins such as the uncoupling proteins and adenine nucleotide translocase. Using mitochondria from rat liver, which lack uncoupling proteins, in the present study we show that energization (specifically, high membrane potential) is required for 4-hydroxynonenal to activate proton conductance mediated by adenine nucleotide translocase. Prolonging the time at high membrane potential promotes greater uncoupling. 4-Hydroxynonenal-induced uncoupling via adenine nucleotide translocase is prevented but not readily reversed by addition of carboxyatractylate, suggesting a permanent change (such as adduct formation) that renders the translocase leaky to protons. In contrast with the irreversibility of proton conductance, carboxyatractylate added after 4-hydroxynonenal still inhibits nucleotide translocation, implying that the proton conductance and nucleotide translocation pathways are different. We propose a model to relate adenine nucleotide translocase conformation to proton conductance in the presence or ab...Continue Reading

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Citations

Aug 26, 2009·Journal of Bioenergetics and Biomembranes·Nadeene ParkerMartin D Brand
Oct 15, 2013·Trends in Biochemical Sciences·Ryan J MaillouxMary-Ellen Harper
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May 11, 2016·Trends in Plant Science·Chun Pong Lee, A Harvey Millar
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Mar 20, 2021·Reproduction in Domestic Animals = Zuchthygiene·Ying LiuShuang Liang
Jun 11, 2021·Journal of Applied Physiology·Daniele A CardinaleFilip J Larsen
Sep 1, 2021·Molecular and Cellular Biochemistry·Edilburga Reyes-JiménezVerónica Rocío Vásquez-Garzón

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