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The University of Southampton
Biological Sciences

Mitochondria-Targeted Bioactive Molecules and Redox Probes Seminar

Time:
17:00
Date:
19 November 2012
Venue:
Building 85 Room 2207

For more information regarding this seminar, please telephone Beatrice Murphy on 023 8059 5374 or email B.J.Murphy@southampton.ac.uk .

Event details

Mitochondrial production of reactive oxygen species (ROS) contributes to many cell processes. Consequently there is a need to develop specific tools to manipulate mitochondrial ROS production and oxidative damage. Here I report on the development of novel antioxidants that selectively block some aspects of mitochondrial oxidative damage, enabling the roles of mitochondrial oxidative stress to be inferred.

One of these antioxidants, MitoQ, is an ubiquinone derivative targeted to mitochondria by covalent attachment to a lipophilic triphenylphosphonium cation through an aliphatic carbon chain. Due to the large mitochondrial membrane potential, the cation was accumulated within mitochondria inside cells, where the ubiquinone moiety inserted into the lipid bilayer and was reduced by the respiratory chain. The ubiquinol derivative thus formed was an effective antioxidant that prevented lipid peroxidation and protected mitochondria from oxidative damage. In cell culture studies, the mitochondrially-localized antioxidant protected mammalian cells from hydrogen peroxide-induced apoptosis. This was compared to untargeted ubiquinone analogs which were ineffective in preventing apoptosis. Selectively manipulating mitochondrial antioxidant status with targeted antioxidants is a feasible approach to investigate the role of mitochondrial oxidative damage in cell death. In addition to MitoQ, a range of other mitochondria targeted redox probes and antioxidants have since been developed. This approach may have further applications in investigating mitochondrial dysfunction in a range of experimental models.

Mitochondria

Speaker information

Dr Mike Murphy, MRC Mitochondrial Biology Unit. Cambridge

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