MICROTUBULE-ACTIVE DRUGS SUPPRESS THE CLOSURE OF THE PERMEABILITY TRANSITION PORE IS TUMOR MITOCHONDRIA

We report the effects of anticancer drugs, inhibitors of microtubule o rganisation, on the mitochondrial permeability transition pore (PTP) i n Ehrlich ascites tumour cells, Taxol (5-20 mu M) and colchicine (100- 500 mu M) prevented closing of the cyclosporin A-sensitive PTP, No tax ol or colchicine effects on oxidative phosphorylation were observed in the range of concentrations used. We suggest that either membrane-bou nd tubulin per se can be part of PTP and/or the attachment of mirochon dria to the microtubular network is essential for PTP regulation. The taxol inhibition of PTP closure, mediated through interaction with the cytoskeleton, sheds new light on the cytotoxic properties of this ant icancer drug.