Protonation Equilibrium of Ellipticine Bound to the Energy-Transducing Membrane of Mitochondria

The relationship between the protonation state of ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole), an antitumoral alkaloid, and the transmembrane proton electrochemical gradient associated with mitochondrial membranes has been investigated. The binding parameters of ellipticine to mitochondria are independent of either the transmembrane ΔpH or membrane potential, which are both components of protongradient (association constant=1.5×10 6 M -1 ; maximal binding ratio=one bound ellipticine per 25 phospholipids). Since the apparent pK of bound ellipticine is 7.1, its two protonation states can be detected from their specific fluorescence emission spectra near physiological pH