The lack of an effect of OP2113 on mitochondrial oxidative phosphorylation.

Abstract

Panel A: This diagram illustrates a classical respiration assay and presents O2 concentration (solid lines) and O2 consumption slope (dotted lines) of rat heart mitochondria after a short incubation in the presence of the vehicle (blue lines) or 80 μM OP2113 (red lines). Respiratory substrates (glutamate + malate in this assay) were added, triggering the onset of oxygen consumption (substrate state, blue background) and then phosphorylation was promoted by the addition of 1 mM ADP in order to obtain the maximal oxidative phosphorylation rate (State 3, red background) [4, 35]. Finally, atractyloside (ATR), which inhibits the ADP/ATP translocator, was added to yield the mitochondrial leak rate (green background) under non phosphorylating conditions (State 4). Panels B to D: The three energetic states were studied in the presence of increasing concentrations of OP2113 (5, 20, and 80 μM), and with mitochondria oxidizing different respiratory substrate combinations: glutamate + malate (B), which feeds electrons to complex I; succinate in the presence of rotenone (C), supplying electrons to complex II; and glutamate + malate + succinate (D) feeding electrons to both complexes I & II. Results are based on 3 independent experiments. No significant differences in mitochondrial respiration rates were noted after the addition of OP2113.</p