title: Impact of mitochondriotropic quercetin derivatives on mitochondria.
abstract: Mitochondria-targeted polyphenols are being developed with the intent to intervene on the levels of reactive oxygen species (ROS) in mitochondria. Polyphenols being more than just anti-oxidants, the interaction of these derivatives with the organelles needs to be characterised. We have studied the effects of two quercetin derivatives, 3-(4-O-triphenylphosphoniumbutyl)quercetin iodide (Q3BTPI) and its tetracetylated analogue (QTA3BTPI), on the inner membrane aspecific permeability, transmembrane voltage difference and respiration of isolated rat liver mitochondria. While the effects of low concentrations were too small to be reliably defined, when used in the 5-20 microM range these compounds acted as inducers of the mitochondrial permeability transition (MPT), an effect due to pro-oxidant activity. Furthermore, Q3BTPI behaved as an uncoupler of isolated mitochondria, causing depolarisation and stimulating oxygen consumption. When applied to tetramethylrhodamine methyl ester (TMRM)-loaded HepG2 or Jurkat cells uptake of the compounds was predictably associated with a loss of TMRM fluorescence, but there was no indication of MPT induction. A production of superoxide could be detected in some cells upon prolonged incubation of MitoSOX-loaded cells with QTA3BTPI. The overall effects of these model mitochondriotropic polyphenols may thus differ considerably depending on whether their hydroxyls are protected or not and on the experimental system. In vivo assays will be needed for a definitive assessment of their bioactivities.
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy; Department of Chemical Sciences, University of Padova, Padova, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Biasutto
authors.forename: Nicola
authors.initials: N
authors.lastname: Sassi
authors.forename: Andrea
authors.initials: A
authors.lastname: Mattarei
authors.forename: Ester
authors.initials: E
authors.lastname: Marotta
authors.forename: Paola
authors.initials: P
authors.lastname: Cattelan
authors.forename: Antonio
authors.initials: A
authors.lastname: Toninello
authors.forename: Spiridione
authors.initials: S
authors.lastname: Garbisa
authors.forename: Mario
authors.initials: M
authors.lastname: Zoratti
authors.forename: Cristina
authors.initials: C
authors.lastname: Paradisi
mesh_terms: D000818:Animals; D004566:Electrodes; D005453:Fluorescence; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption; D011794:Quercetin / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D012119:Respiration / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D013481:Superoxides; D011794:Quercetin