This procedure allows the monitorization of respiration. This method is useful for identify compounds that regulate the activity of the UCPs. These compunds would be potential drugs to treat obesity or as antipyretic.

High throughput screening procedure

Mitochondria are the cellular organelles where ATP is produced from the energy released during the oxidation of sugars and lipids. This process, termed oxidative phosphorylation, can be divided in two parts: respiration (substrate oxidation) and ATP synthesis. Both are coupled in such way that rate of substrate oxidation is adjusted to cellular demand for ATP synthesis. This coupling has important implications for cellular economy since reserves are not wasted.

However, certain physiological situations require energy dissipation. Maintenance of body temperature is one example: in mammals non- shivering thermogenesis is achieved by uncoupling oxidative phosphorylation. This mechanism is also used to eliminate excess calories ingested with the diet. Energy dissipation is important to lower the rate of free radical production, these reactive species cause cell damage that can eventually lead to cell death. The proteins that catalyse this energy dissipation are termed uncoupling proteins (UCP).

We have developed a procedure to determine the rate of mitochondrial respiration, applicable to evaluate the ability of compounds to modulate the activity of the UCP, since changes in UCP activity necessarily lead to changes in the rate of mitochondrial respiration . This compounds could become potential drugs for treating diseases due to changes in thermogenic activity of tissues where these proteins are present  (diabetes, hypertension, cachexia).

INNOVATIVE ASPECTS

The method is a high throughput screening procedure that presents important advantages compared to existing protocols. Identification of new therapeutic compounds (obesity, diabetes, development of new antipyretics, etc.) with this method is easy, cheap, highly reproducible and useful to process high number of samples.

COMPETITIVE ADVANTAGES

This procedure is highly suitable to screen a large number of compounds.

Early Stage

Research under contract or research collaboration