Post by David Feder on Jun 11, 2009 18:28:10 GMT -5
Quercetin can act either as an inhibitor or an inducer of the
Mitochondrial Permeability Transition Pore:
a demonstration of the ambivalent redox character of polyphenols
Umberto De Marchi,1 Lucia Biasutto,1,2 Spiridione Garbisa,1 Antonio Toninello3 and
Mario Zoratti1,4,*
Departments of 1Biomedical Sciences, 2Chemical Sciences and 3Biological Chemistry, University of Padova,
and 4CNR Institute of Neuroscience, Padova, Italy
Abstract
The Ca2+- and oxidative stress-induced Mitochondrial Permeability Transition (MPT) plays an
important role in phenomena ranging from tissue damage upon infarction to muscle wasting in
some forms of dystrophy. The process is due to the activation of a large pore in the inner
mitochondrial membrane. Antioxidants are considered a preventive and remedial tool, and
mitochondria-targeted redox-active compounds have been developed. Plant polyphenols are
generally considered as antioxidants, and thus candidates to the role of mitochondria-protecting
agents. In patch-clamp experiments, easily oxidizable polyphenols induced closure of the channels.
In swelling experiments with suspensions of mitochondria, high (20-50 ìM) concentrations of
quercetin, the most efficient inhibitor, promoted instead the onset of the MPT. Chelators of Fe2+/3+
and Cu+/2+ ions counteracted this effect. Fluorescent indicators of superoxide production confirmed
that quercetin potentiates O2
·- generation by isolated mitochondria and cultured cells. Since this was
not affected by chelating Fe and Cu ions, the MPT-inducing effect can be ascribed to a “secondary”,
metal ion-catalyzed production of ROS. These results are a direct demonstration of the ambivalent
redox character of polyphenols. Their mode of action in vivo cannot be taken for granted, but needs
to be experimentally verified.
Mitochondrial Permeability Transition Pore:
a demonstration of the ambivalent redox character of polyphenols
Umberto De Marchi,1 Lucia Biasutto,1,2 Spiridione Garbisa,1 Antonio Toninello3 and
Mario Zoratti1,4,*
Departments of 1Biomedical Sciences, 2Chemical Sciences and 3Biological Chemistry, University of Padova,
and 4CNR Institute of Neuroscience, Padova, Italy
Abstract
The Ca2+- and oxidative stress-induced Mitochondrial Permeability Transition (MPT) plays an
important role in phenomena ranging from tissue damage upon infarction to muscle wasting in
some forms of dystrophy. The process is due to the activation of a large pore in the inner
mitochondrial membrane. Antioxidants are considered a preventive and remedial tool, and
mitochondria-targeted redox-active compounds have been developed. Plant polyphenols are
generally considered as antioxidants, and thus candidates to the role of mitochondria-protecting
agents. In patch-clamp experiments, easily oxidizable polyphenols induced closure of the channels.
In swelling experiments with suspensions of mitochondria, high (20-50 ìM) concentrations of
quercetin, the most efficient inhibitor, promoted instead the onset of the MPT. Chelators of Fe2+/3+
and Cu+/2+ ions counteracted this effect. Fluorescent indicators of superoxide production confirmed
that quercetin potentiates O2
·- generation by isolated mitochondria and cultured cells. Since this was
not affected by chelating Fe and Cu ions, the MPT-inducing effect can be ascribed to a “secondary”,
metal ion-catalyzed production of ROS. These results are a direct demonstration of the ambivalent
redox character of polyphenols. Their mode of action in vivo cannot be taken for granted, but needs
to be experimentally verified.