UC San Diego

Nearly 20 years ago, mitochondria were mistakenly considered only as the home production of energy molecule, adenosine triphosphate. However, a large growing research body has uncovered numerous vital roles of the mitochondria in various biological processes, such as aging, signaling, immunity, calcium homeostasis, and diseases including diabetes, cancer, and Parkinson’s disease.Mitochondrial dysfunction could result from mutation of its genetic component. It’s quite tricky to relate mitochondrial dysfunction with certain pathogenic phenotype. Thus, metabolomic study was conducted to reveal causal metabolites, and classify their association with various symptoms. The untargeted metabolomic study was performed in favor of the detection of bioactive lipid in the plasma of approximately two thousand patients with genetic mitochondrial diseases. Bioactive lipids are major chemical class in the body, containing inflammatory meditated lipids. Our studies on this topic led to the discovery of new hydroxyl fatty acid family that has been associated with mitochondrial diseases. Mitochondria, on the other hand, have involved in cancer, and they are considered a great potential therapeutic target for the initiation of death pathway, and hence, it leads to the apoptosis of cancerous cells. Caged Garcinia xanthones (CGXs), which are natural products, have been identified as potent antitumor agents targeting the mitochondria. On this topic, we synthesized forbesione, a member of the CGX family, and various synthetic analogs in order to potentially produce more potent analogs compared to the parent compound.