title: Accumulation of dodecyltriphenylphosphonium in mitochondria induces their swelling and ROS-dependent growth inhibition in yeast.
abstract: Hydrophobic cations with delocalized charge are used to deliver drugs to mitochondria. However, micromolar concentrations of such compounds could be toxic due to their excessive accumulation in mitochondria. We studied possible pathophysiological effects of one such cation, i.e. dodecyltriphenylphosphonium (C(12)-TPP), in the yeast Saccharomyces cerevisiae. First, we found that C(12)-TPP induces high-amplitude mitochondrial swelling. The swelling can be prevented by addition of protonophorous uncoupler FCCP or antioxidant alpha-tocopherol, but not other tested antioxidants (N-acetylcysteine and Trolox). Second, FCCP prevents ROS-sensitive fluorescent dye (dichlorofluorescein diacetate) staining of yeast treated with C(12)-TPP. We also showed that all tested antioxidants partially restore the growth inhibited by C(12)-TPP. The latter points that ROS rather than the mitochondria swelling limit the growth rate.
authors.affiliation: Moscow State University, Vorobyevy Gory, Russia.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Ojovan
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Knorre
authors.forename: Olga V
authors.initials: OV
authors.lastname: Markova
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Smirnova
authors.forename: Lora E
authors.initials: LE
authors.lastname: Bakeeva
authors.forename: Fedor F
authors.initials: FF
authors.lastname: Severin
mesh_terms: D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development*; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D009943:Organophosphorus Compounds; D017382:Reactive Oxygen Species; D014475:Uncoupling Agents; C001115:dodecyltriphenylphosphonium; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone