Abstract

The uncoupling of oxidative phosphorylation in mitochondria, a process critical for thermogenesis and metabolic regulation, can be induced by various agents, including fatty acids and their derivatives. This study investigates the specific mechanism by which $\omega$-hydroxypalmitic acid (HPA), a $\omega$-oxidation product of palmitic acid, exerts its ionophore uncoupling action in isolated rat liver mitochondria. HPA is known to act as a protonophore, dissipating the mitochondrial membrane potential ($\Delta\Psi$) and thus uncoupling the electron transport chain from ATP synthesis. The objective of this research was to determine the involvement of the mitochondrial phosphate carrier (PiC), an inner membrane transporter essential for oxidative phosphorylation, in this process. Using established methods of polarography and $\Delta\Psi$ measurement, the effect of HPA on mitochondrial respiration and membrane potential was analyzed in the presence and absence of PiC inhibitors. The results demonstrate that the ionophore uncoupling effect of HPA is significantly modulated by the activity of the phosphate carrier. This suggests that the PiC does not merely transport phosphate but also participates in the transport cycle of HPA or its complex with a cation, facilitating the proton leak across the inner mitochondrial membrane. These findings highlight a novel, non-canonical role for the phosphate carrier in the uncoupling mechanism of $\omega$-hydroxypalmitic acid, providing critical insight into the regulation of mitochondrial bioenergetics and the potential therapeutic targets for metabolic disorders.