Hamster Brown‐Adipose‐Tissue Mitochondria

TLDR

The inner membrane of hamster brown adipose tissue mitochondria possesses a proton/hydroxyl ion and halide anion conductance that can be specifically inhibited by exogenous purine nucleoside di‑ or triphosphates, a pathway implicated in the physiological control of non‑shivering thermogenesis. The study investigates the mechanism by which nucleotides interact with this mitochondrial conductance pathway. Added nucleotides inhibit the ion conductances directly, without equilibrating with the matrix pools of purine nucleotides. The authors identified a distinct purine nucleotide binding site (≈0.7 nmol mg⁻¹) that, when occupied by nucleotides, inhibits the conductance pathway without covalent modification; ADP translocation is fully sensitive to atractylate, GDP translocation is absent, and the site is absent in rat liver mitochondria, indicating a causal link between nucleotide binding and conductance inhibition.

Abstract

The inner membrane of hamster brown adipose tissue mitochondria possesses a mechanism for the conductance of protons (or hydroxyl ions) and halide anions which may be specifically inhibited by exogenous purine nucleoside di‐ or triphosphates. The mechanism of the nucleotide interaction is examined. The added nucleotides can inhibit the ion conductances without equilibrating with the matrix pools of purine nucleotides. ADP translocation is completely sensitive to atractylate, and no mechanism for GDP translocation could be detected. The nucleotides act on the conductance mechanism without covalent modification. A purine nucleotide binding site is described which is distinct from the adenine nucleotide translocase, does not bind atractylate, has a capacity of 0.7 nmol · mg −1 , and affinities, specificities and a pH dependency closely corresponding to the conditions required for the inhibition of the ion conductances. The binding site is not apparent in rat liver mitochondria. A causal relationship is suggested between the occupation of this site by added purine nucleotides, and the inhibition of the ion conductance pathway. The role of the pathway in the physiological control of non‐shivering thermogenesis by the tissue is discussed.