Mechanism of primary Cd2+-induced rat liver mitochondria dysfunction: discrete modes of Cd2+ action on calcium and thiol-dependent domains

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

“…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]. DNP-stimulated respiration was not affected by Tl…”

“…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].…”

“…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].…”

Hypoxia-cadmium interactions on rainbow trout (Oncorhynchus mykiss) mitochondrial bioenergetics: attenuation of hypoxia-induced proton leak by low doses of cadmium

“…Mitochondrial uncouplers such as DNP shuttle protons from the inter-membrane space into the matrix, increasing oxygen consumption and dissipating the Δp without causing damage to the mitochondrial membrane or ETC. Thus inhibition of the uncouplerstimulated respiration is indicative of impaired ETC (Belyaeva and Korotkov, 2003). Importantly, the impairment of ETC was directly confirmed by enzyme activity measurements that revealed a greatly reduced complex I activity (Fig.…”

“…Although the cellular targets and toxic effects of Cd are numerous, the mitochondrion is arguably the most important target site of its toxic action. In this regard, extant literature indicates that several aspects of the three mitochondrial subsystems -phosphorylation, substrate oxidation and proton leak -are impacted by Cd (Kesseler and Brand, 1994;Belyaeva and Korotkov, 2003;Cannino et al, 2009;Kurochkin et al, 2011;Adiele et al, 2012;Ivanina et al, 2012).…”