Increase in the toxic effects of Tl⁺ on isolated rat liver mitochondria in the presence of nonactin

Abstract

The effects of Tl(+) ions on isolated rat liver mitochondria were studied in the presence of nonactin, a cyclic ionophore. Nonenergized rat liver mitochondria were increasingly swollen at an elevated concentration of Tl(+) in the 160 mOsm medium containing 0-150 mM sucrose and 0-75 mM TlNO(3) or 0-50 mM Tl acetate. On the contrary, mitochondria in experiments with nonactin were contracted in the medium with 5-25 mM Tl(+) and were swollen only in the medium with 50-75 mM TlNO(3) or 50 mM Tl acetate. State 4 respiration along with swelling of succinate-energized mitochondria followed contraction after their deenergization was further enhanced at increasing concentration of Tl acetate in a medium containing nonactin. Regardless of the presence of nonactin, State 3 and 2,4-dinitrophenol (DNP)-stimulated respiration and the monoamine oxidase (MAO) activity were not affected in the medium with 0-25 mM Tl acetate and sucrose. DNP-stimulated respiration decreased and the MAO activity somewhat increased in the medium containing 50 mM Tl acetate and nonactin. Uptake of (86)Rb(+) by energized mitochondria in the presence of valinomycin was considerably decreased when Tl(+) and nonactin were simultaneously present in the medium. An increase of the toxic effect of Tl(+) on rat liver mitochondria in the presence of nonactin is accounted for by disruption of mitochondria due to their more extensive swelling and uncoupling of mitochondria, resulting in the stimulation of State 4 and depletion of their energy store.

Inorganic phosphate stimulates the toxic effects of Tl+ in rat liver mitochondria

“…Nonenergized mitochondria demonstrated massive swelling in the Tl acetate medium [6,7] by Tl + /H + exchange [7]. Further massive swelling of the mitochondria was found after their energization [3,6,7,12]. The swelling is accounted for by electrophoretic uniport of Tl + in the matrix [3,7,11].…”

“…It was shown that Tl + increased state 4 of rat liver mitochondria [2][3][4][5][6] followed by their uncoupling [3,6,7]. At the same time, no marked effect of Tl + on state 3 and 2,4-dinitrophenol(DNP)-stimulated respiration [2][3][4]6] and on mitochondrial respiratory enzymes [3,[8][9][10] was found. Considering that the inner mitochondrial membrane is easily permeable to Tl + [3,11], nonenergized mitochondria can markedly swell in TlNO 3 medium [6,7,12].…”

“…Subsequent energization of the mitochondria stimulated their contraction through the Tl + /H + exchange mechanism [6,7]. Nonenergized mitochondria demonstrated massive swelling in the Tl acetate medium [6,7] by Tl + /H + exchange [7]. Further massive swelling of the mitochondria was found after their energization [3,6,7,12].…”

“…Considering that the inner mitochondrial membrane is easily permeable to Tl + [3,11], nonenergized mitochondria can markedly swell in TlNO 3 medium [6,7,12]. Subsequent energization of the mitochondria stimulated their contraction through the Tl + /H + exchange mechanism [6,7]. Nonenergized mitochondria demonstrated massive swelling in the Tl acetate medium [6,7] by Tl + /H + exchange [7].…”

“…At the same time, no marked effect of Tl + on state 3 and 2,4-dinitrophenol(DNP)-stimulated respiration [2][3][4]6] and on mitochondrial respiratory enzymes [3,[8][9][10] was found. Considering that the inner mitochondrial membrane is easily permeable to Tl + [3,11], nonenergized mitochondria can markedly swell in TlNO 3 medium [6,7,12]. Subsequent energization of the mitochondria stimulated their contraction through the Tl + /H + exchange mechanism [6,7].…”