Effect of TRO19622 (Olesoxime) on the Functional Activity of Isolated Mitochondria and Cell Viability

TRO19622 (olesoxime), a cholesterol-like cytoprotector, is an experimental drug developed as a potential treatment for a range of incurable degenerative diseases. Recent studies have shown that the main molecular targets of this compound in the cell are porins of the outer mitochondrial membrane, which play a crucial role in regulating the exchange of metabolites between mitochondria and the rest of the cell. Disruption of this channel activity may lead to mitochondrial dysfunction in healthy cells. In this study, key indicators of mitochondrial function and the viability of cells in cultures after incubation with TRO19622 were assessed. It was found that TRO19622 at 15–30 μM concentrations inhibits the coupled and uncoupled respiration rates in isolated mitochondria (state 3 rate and 3UDNP) with succinate as substrate, but does not affect the enzymatic activity of respiratory chain complexes I–IV. It was shown that TRO19622 at the studied doses has no effect on the rate of H2O2 formation in mitochondria and the calcium retention capacity index, which reflects the resistance of the organelles to the calcium-dependent nonspecific pore opening. Incubation of human skin fibroblasts and mammary adenocarcinoma cells (MCF-7) with 30 μM TRO19622 for 48 h has no impact on ROS production and cell viability. How TRO19622 works in the oxidative phosphorylation system and therapeutic prospects for using this mitochondrial-targeted agent are discussed.