Inner membrane anion channel and dicarboxylate carrier in brown adipose tissue mitochondria
Jezek, P.; Borecký, J.
International Journal of Biochemistry and Cell Biology 28(6): 659-666
ISSN/ISBN: 1357-2725 PMID: 8673730 DOI: 10.1016/1357-2725(96)00008-8
In brown adipose tissue mitochondria, the anion transport proteins should respond to regulatory mechanisms controlling the thermogenic or resting state. We re-evaluated the role of transport of organic/metabolite anions in these mitochondria, namely with regards to DELTA-pH-regulation and substrate specificity. Valinomycin-induced osmotic swelling in potassium salts indicated by light scattering either directly on a fluorometer, or as the reciprocal absorbance, was used to characterize the anion uniport. A DELTA-pH "jump" was thus created in respiring mitochondria and the DELTA-pH-driven transport was studied. The two major features are reported: (1) existence of the inner membrane anion channel exhibiting the same full spectrum of anion and inhibitor specificity as in liver; and (2) existence of dicarboxylate carrier, so far disputed in brown adipose tissue mitochondria. The inner membrane anion channel was activated either by elevating DELTA-pH in respiring mitochondria or by depleting matrix Mg-2+ at alkaline pH. Dicarboxylate carrier was activated by elevated DELTA-pH under conditions when the channel was blocked. A specific DELTA-pH regulation could explain this activation and silence of the carrier in early studies. In conclusion, wide substrate specificity makes the inner membrane anion channel suitable for the regulation of volume homeostasis and a feed-back control between the DELTA--PSI-driven and the DELTA-pH-driven transport. The DELTA-pH-activated dicarboxylate carrier is essential in the coupled state for malate uptake which enables fatty acid synthesis, while, in the uncoupled state, inaccessibility of dicarboxylates favors oxidation of fatty acids or pyruvate.