Structural and Functional Features of [Ca.sup.2+] Transport Systems in Liver Mitochondria of Rats with Experimental Hyperthyroidism

We analyzed structural and functional features of the main mitochondrial [Ca.sup.2+]-transporting systems, mitochondrial [Ca.sup.2+] uniporter complex (MCUC) and [Ca.sup.2+]-dependent cyclosporin A-sensitive mitochondrial permeability transition pore (MPT pore), in rats with hyperthyroid state. It was found that, the rate of [Ca.sup.2+] accumulation by rat liver mitochondria in this pathology increases by 1.3 times, which can be associated with higher level of the channelforming subunit of the uniporter MCU and lower content of dominant-negative subunit of this complex MCUb. At the same time, the level of the regulatory subunit MICU1 remained unchanged. It was shown that calcium retention capacity of liver mitochondria in rats with experimental hyperthyroidism decreased by 2 times in comparison with the control, which attested to reduced resistance of liver mitochondria of hyperthyroid rats to induction of the MPT pore. The observed changes are consistent with the data on increased amount of cyclophilin D, a mitochondrial matrix peptidyl-prolyl isomerase that is known to modulate the MPT pore opening and expression of the Ppif gene that encodes mitochondrial cyclophilin D in rats with experimental hyperthyroidism. Key Words: hyperthyroidism; mitochondria; mitochondrial [Ca.sup.2+] uniporter; [Ca.sup.2+]-induced mitochondrial permeability transition pore; cyclophilin D