The role of mitochondrial uncoupling proteins in regulation of reactive oxygen species

• Applicant: Professorin Dr. Elena E. Pohl
• Subject Area: Anatomy and Physiology
• Term: from 2007 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 36575480

Reactive oxygen species (ROS) produced during mitochondrial respiration are a major cause of the cellular oxidative damage that may underlie neurodegenerative diseases and ageing. Their production is very sensitive to the mitochondrial proton-motive force and may be decreased by uncoupling. In turn, ROS are hypothesized to affect UCP, increasing (i) UCP proton transport rate and (ii) protein abundance. To prove both hypotheses, we measure (i) proton currents through the purified protein reconstituted in planar bilayer membranes and (ii) mRNA and UCP levels in neuronal cells, using RT PCR and confocal microscopy. UCP protection against oxidative damage is evaluated by estimation of ROS amount and mitochondrial potential using fluorescent dyes in cells with different expression levels of protein. To reveal a functional link between uncoupling and protection against oxidative damage, UCPs with various putative functions (UCP1, UCP2, UCP4) are investigated. Differentiation between ROS-mediated UCP activation and upregulation as well as insight into ROS regulation by UCP are expected to provide the basis for a rational drug design, and have, thus, important clinical implications.

• DFG Programme: Research Grants
• International Connection: Austria