Abstract
Andrew L. Niles
Promega Corporation, 2800 Woods Hollow Road, Madison WI 53711
Recent trends within the in vitro safety and toxicology screening community suggest value in indentifying pathway-dependent cytotoxic burdens more proximal to the actual test compound insult. Mitochondria are key early beacons of potential cytotoxicity because they control the critical functions of producing the preponderance of cellular energy as well as modulating apoptotic programs. Although elegant systems exist for measuring mitochondrial dysfunction, the existing technologies are poorly accessible due to expense, requisite instrumentation and consumables, and have low throughput. Here we demonstrate a simple, rapid, sensitive, cost-effective and predictive, cell-based, multiplexed method to assess and triage potential mitochondrial toxicities from large chemical libraries or medicinal modification efforts. The assay is predicated upon the use of ATP and membrane integrity biomarkers to assess mitochondrial dysfunction.