Abstract

Mitochondrial Metabolomics: Identifying Early in-vivo Biochemical Markers of Mitochondrial Toxicity

James R Armitage, Senior Scientist, GSK

Standard in-vivo pre-clinical toxicology testing relies on the use of animals which are generally young and metabolically healthy; as such they are relatively insensitive to compound-mediated mitochondrial perturbation, often remaining asymptomatic. This contrasts with patients whose metabolic capacity is often compromised by many factors including age, lifestyle, co-medication, disease etc, where a mild mitochondrial insult could result in a severe clinical effect. There are currently no easily accessible biomarkers to monitor compound-mediated effects on mitochondria in-vivo, from either a toxicology or pharmacology perspective. An innovative and carefully designed study using a known potent electron transport chain inhibitor was employed to identify metabolites that change in advance or absence of a clinical effect to identify potential biochemical indicators of underlying mitochondrial function.