Regulation of Mitochondrial Metabolism by Reversible Lysine Acylation
A core focus of our laboratory studies is mitochondrial fatty acid oxidation (FAO), the pathway by which fatty acids are broken down for energy. Mutations in the FAO genes are among the most prevalent inborn errors of metabolism. Recently, it was discovered that the FAO enzymes are heavily modified by post-translational modifications, including lysine acetylation and lysine succinylation. There are three mitochondrial sirtuin deacylases (SIRT3, SIRT4, SIRT5), which are believed to reverse some of these modifications. The lab’s current research focuses on the functional effects of lysine acetylation and succinylation on the FAO pathway and the role the sirtuins play in regulating metabolism.
Cancer Metabolism
Otto Warburg observed in 1924 that cancer cells have an unusual reliance on glycolysis for energy. He believed this metabolic switch to be indicative of a defect in mitochondrial oxidative metabolism. More than 90 years later, researchers still do not understand how and why cancer cells alter their metabolism or what role changes in mitochondrial energy metabolism play in the etiology of cancer or in the ability of cancer cells to escape apoptosis. Answering these questions may reveal cancer’s Achilles’ heel and lead to a cure. A new project in the lab is focusing on the role of the sirtuin deacetylase SIRT2 in regulating the Warburg effect during the progression of liver cancer.