title: Electrically wired mitochondrial electrodes for measuring mitochondrial function for drug screening.
abstract: In the continual search of new therapeutics, many possible drug candidates are excluded, because they are found to negatively affect mitochondrial function. We have developed an approach for directly, electrochemically assaying mitochondrial metabolic activity as a function of metabolic substrate to determine drug toxicity. By wiring mouse mitochondria to a carbon electrode surface, electrons can be intercepted before they reach Complex IV, the terminal step of electron transport chain. The electrons are rerouted, to a separate electrode of the electrochemical cell, the cathode. This allows for the direct measurement of electrical current and potential of the mitochondria during their oxidation of substrates such as pyruvate and fatty acids when there are different concentrations of drug present. This analytical technique has been shown to reliably assay several classical mitochondrial toxins and exhibits potential for the further development of a drug candidate screening technique, as well as other applications where the quantitative study of mitochondrial dysfunction is important.
authors.affiliation: Department of Chemistry, Saint Louis University, St. Louis, MO 63103, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Arechederra
authors.forename: Abdul
authors.initials: A
authors.lastname: Waheed
authors.forename: William S
authors.initials: WS
authors.lastname: Sly
authors.forename: Shelley D
authors.initials: SD
authors.lastname: Minteer
mesh_terms: D000818:Animals; D002244:Carbon / Q000737:chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D055664:Electrochemical Techniques; D004566:Electrodes; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D019289:Pyruvic Acid / Q000737:chemistry / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D004364:Pharmaceutical Preparations; D002244:Carbon; D019289:Pyruvic Acid; D003576:Electron Transport Complex IV