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The Mechanisms of Fatty Acid-Induced Proton Permeability of the Inner Mitochondrial Membrane

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Abstract

Nonesterified long-chain fatty acids have long been known as uncouplers of oxidativephosphorylation. They are efficient protonophores in the inner mitochondrial membrane but not so inartificial phospholipid membranes. In the un-ionized form, they undergo a rapid spontaneoustransbilayer movement (flip-flop). However, the transbilayer passage of the dissociated(anionic) form is hindered by the negatively charged hydrophilic carboxylic group. In theinner mitochondrial membrane, the transfer of fatty acid anions is mediated by the adeninenucleotide translocase, the dicarboxylate carrier, and the glutamate/aspartate carrier. As a result,the passage of protons and electric charges is a concerted effect of the spontaneous flip-flopof the undissociated (protonated) form in one direction and carrier-facilitated transfer of theionized (deprotonated) form in the other direction. In addition, fatty acids also promote openingof the mitochondrial permeability transition pore, presumably due to their interaction with oneof its constituents, the adenine nucleotide translocase, thus forming an additional route fordissipation of the proton gradient. Structural prerequisites for these proton-conductingmechanisms are (1) a weakly ionized carboxylic group and (2) a hydrocarbon chain of appropriatelength without substituents limiting its mobility and hydrophobicity.

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  1. Nencki Institute of Experimental Biology, Pasteura 3, 02-093, Warsaw, Poland

    Lech Wojtczak & Mariusz R. Wie¸ckowski

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  1. Lech Wojtczak
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Wojtczak, L., Wie¸ckowski, M.R. The Mechanisms of Fatty Acid-Induced Proton Permeability of the Inner Mitochondrial Membrane. J Bioenerg Biomembr 31, 447–455 (1999). https://doi.org/10.1023/A:1005444322823

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