Derivatives of Rhodamine 19 as Mild Mitochondria-targeted Cationic Uncouplers

• DOI: 10.1074/jbc.m110.212837
• Publication Date: 2011-03-31T00:18:08Z
• Authors: Yuri N. Antonenko; Armine V. Avetisyan; Dmitry A. Cherepanov; Dmitry A. Knorre; Galina A. Korshunova; Olga V. Markova; Silvia M. Ojovan; Irina V. Perevosh...; Antonina V. Pusto...; Tatyana I. Rokits...; Inna I. Severina; Ruben A. Simonyan; Ekaterina A. Smir...; Alexander A. Sobko; Natalia V. Sumbatyan; Fedor F. Severin; Vladimir P. Skula...
• Keywords: Protonophore; Rhodamine 123; Nigericin; Rhodamine; Efflux

A limited decrease in mitochondrial membrane potential can be beneficial for cells, especially under some pathological conditions, suggesting that mild uncouplers (protonophores) causing such an effect are promising candidates therapeutic uses. The great majority of protonophores weak acids capable permeating across membranes their neutral and anionic forms. In the present study, protonophorous activity a series derivatives cationic rhodamine 19, including dodecylrhodamine (C(12)R1) its conjugate with plastoquinone (SkQR1), was revealed using variety assays. Derivatives B, lacking dissociable protons, showed no properties. planar bilayer lipid membranes, separating two compartments differing pH, diffusion H(+) ions generated presence C(12)R1 SkQR1. These compounds induced pH equilibration liposomes loaded probe pyranine. SkQR1 partially stimulated respiration rat liver mitochondria State 4 decreased potential. Also, yeast cells but, unlike protonophore FCCP, did not suppress growth. Loss function DNA (grande-petite transformation) is known to cause major We found petite relatively more sensitive than compared grande cells. Together, our data suggest 19-based self-limiting; uncoupling maximal at high potential, but decreases potentials, which causes partial efflux from and, hence, prevents further decrease.