Ubiquinone analogs: a mitochondrial permeability transition pore-dependent pathway to selective cell death.

Ubiquinone analogs: a mitochondrial permeability transition pore-dependent pathway to selective cell death.

Blog Article

Prolonged opening of the mitochondrial permeability transition pore (PTP) leads to cell death.Various ubiquinone analogs have ORG BEET W LEMON JUICE been shown to regulate PTP opening but the outcome of PTP regulation by ubiquinone analogs on cell fate has not been studied yet.The effects of ubiquinone 0 (Ub(0)), ubiquinone 5 (Ub(5)), ubiquinone 10 (Ub(10)) and decyl-ubiquinone (DUb) were studied in freshly isolated rat hepatocytes, cultured rat liver Clone-9 cells and cancerous rat liver MH1C1 cells.PTP regulation by ubiquinones differed significantly in permeabilized Clone-9 and MH1C1 cells from that previously reported in liver mitochondria.Ub(0) inhibited PTP opening in isolated hepatocytes and Clone-9 cells, whereas it induced PTP opening in MH1C1 cells.

Ub(5) did not affect PTP opening in isolated hepatocytes and MH1C1 cells, but it induced PTP opening in Clone-9 cells.Ub(10) regulated PTP in isolated hepatocytes, whereas it did not affect PTP opening in Clone-9 and MH1C1 cells.Only DUb displayed the same effect on PTP regulation in the three hepatocyte lines tested.Despite such modifications in PTP regulation, competition between ubiquinones still occurred in Clone-9 and MH1C1 cells.As expected, Ub(5) induced a PTP-dependent cell death in Clone-9, while it did not affect MH1C1 cell viability.

Ub(0) induced a PTP-dependent cell Earphones death in MH1C1 cells, but was also slightly cytotoxic in Clone-9 by an oxidative stress-dependent mechanism.We found that various ubiquinone analogs regulate PTP in different ways depending on the cell studied.We took advantage of this unique property to develop a PTP opening-targeted strategy that leads to cell death specifically in cells where the ubiquinone analog used induces PTP opening, while sparing the cells in which it does not induce PTP opening.