Cd2+ versus Ca2+-produced mitochondrial membrane permeabilization: a proposed direct participation of respiratory complexes I and III

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

“…This is the reason why swelling of energized mitochondria in K acetate media with Cd 2+ and RR or DTT becomes like that in Tl acetate which is slightly transported in mitochondria [6,7,11]. On the other hand, contraction of the succinate-energized mitochondria swollen in the medium with NH 4 NO 3 and P i , in experiments with Tl + ( Figure 3D, trace 1) is proven to be comparable with that found in experiments with Cd 2+ and DTT [29,30]. Stimulation of state 4 was found in the following experiments: with Tl + ( Figure 5) [3,6], or with K + and VAL [19,32], or with 5-10 μM Cd 2+ , or with 40-60 μM Cd 2+ alongside with RR or DTT [37,41,42].…”

“…Transport of P i in mitochondria was also stimulated by Cd 2+ [28]. State 4 and swelling of mitochondria stimulated by Cd 2+ were substantially increased in the presence of P i [28][29][30]. On the other hand, action of P i on toxic effects of Tl + on mitochondria remains unstudied until now.…”

“…Thus, the available literature data as well as our own results [2][3][4]6,15] (Figures 2-5 and Table 1) allow us to suggest that the toxic effects of Tl + on mitochondria in the presence of P i are not due to interaction of Tl + with the respiratory enzymes and with MAO. It is to be noted that toxic effects of Tl + or of VAL on isolated mitochondria turned out to be comparable with effects of Cd 2+ in the presence of ruthenium red (RR), a potent inhibitor of the mitochondrial Ca 2+ -uniporter [34,35,41], or of dithiothreitol (DTT), an active SH reductant [30,42,43]. Swelling of energized mitochondria in the Tl acetate medium [3,6,7] was comparable with that found in the K acetate media with VAL [3] or with Cd 2+ [34,37,41].…”

“…Cd 2+ , unlike Tl + , has an extremely high affinity to SH groups and thereby inhibits the enzymes [28,36,40]. Cd 2+ decreased state 3 and DNP-stimulated respiration [29,30,37,41,42] and fast discharged mito [43]. Considering the above data, we can conclude that effects of Tl + on DNP-stimulated respiration are mainly due to massive mitochondrial swelling (Figures 2, 3, and 5) [4], but not to inhibition of respiratory enzymes that takes place only in experiments with Cd 2+ [28,30,37,41].…”

“…Cd 2+ decreased state 3 and DNP-stimulated respiration [29,30,37,41,42] and fast discharged mito [43]. Considering the above data, we can conclude that effects of Tl + on DNP-stimulated respiration are mainly due to massive mitochondrial swelling (Figures 2, 3, and 5) [4], but not to inhibition of respiratory enzymes that takes place only in experiments with Cd 2+ [28,30,37,41]. Activity of another mitochondrial enzyme, MAO, was markedly inhibited by Cd 2+ [44] and only somewhat stimulated by Tl + [6,10] regardless of the presence of P i (Table 1).…”