Inhibitors of the ATP/ADP antiporter suppress stimulation of mitochondrial respiration and H⁺ permeability by palmitate and anionic detergents

Abstract

The action of ATP/ADP-antiporter inhibitors upon the uncoupling effect of pahnitate, detergents and 'classical' uncouplers has been studied. The uncoupling effect was estimated by stimulation of succinate oxidation and of Hf permeability of rat liver mitochondria in the presence of oligomytin. It is shown that carboxyatractylate (CAtr) and pyridoxal 5phosphate (PLP) suppress the uncoupling induced by pahnitate and the anionic detergents SDS and cholate, but do not affect that induced by the cationic detergents CTAB, by the non-ionic detergent Triton X-100, as well as by the 'classical' uncouplers FCCP and DNP. The results are discussed in terms of a concept assuming that the ATP/ADP-antiporter facilitates the electrophoretic export of hydrophobic anions from mitochondria.Fatty acid; Uncoupling; ATP/ADP-antiporter

Interaction of adenine nucleotides with the adenine nucleotide translocase regulates the developmental changes in proton conductance of the inner mitochondrial membrane

“…2C), similar to that triggered by ATP ( Fig. 2A), further reinforces the functional homology between UCP and the ATP/ADP antiporter as thermoregulatory elements of uncoupled respiration [15][16][17]22]. At least, under a situation where the adenine nucleotide content of mitochondria is below 30% of its normal level; that is, m the fetal liver [I, 4,5] or under in vitro conditions of adenine nucleotide depletion ( Fig.…”

Long‐chain fatty acid‐promoted swelling of mitochondria: further evidence for the protonophoric effect of fatty acids in the inner mitochondrial membrane

“…The protonophoric activity of FFA [3,4] is limited by a low £ip-£op ability of FFA anions in arti¢cial [5] and mitochondrial membranes [6]. It has been ¢rst reported by the Skulachev's group [3,7] that carboxyatractyloside, a speci¢c inhibitor of the ADP/ ATP carrier, partially reversed the protonophoric activity of FFA in mitochondria. Mainly on this basis Skulachev [8] postulated that the undissociated FFA permeate from the external side of the inner membrane to the matrix side and that the reverse transport of FFA anion is mediated by the ADP/ ATP carrier (fatty acid cycling model) [8].…”

“…For example, the ADP/ATP carrier and the aspartate/glutamate carrier account for only about 25% of the protonophoric activity of the branched chain phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) [13]. Therefore, it seems likely that other up to now unrecognized inner membrane proteins may contribute to the FFA-mediated transmembrane proton transfer.…”

Involvement of mitochondrial inner membrane anion carriers in the uncoupling effect of fatty acids

“…Neverthe less, SDS stimulates mitochondrial respiration similarly to palmitic acid, but in 10 fold higher concentration. Especially important was the finding that the SDS induced stimulation of respiration was sensitive to CAtr [20]. In a study of proton transport in liver mitochondria by the acid pulse method, Brustovetsky showed that both SDS and palmitic acid increased the proton permeability of the inner mitochondrial membrane, and CAtr sup pressed both effects to the same degree [20].…”