Dr. Jurczak’s lab is primarily interested in the relationship between nutrient excess, mitochondrial overload and the pathogenesis of metabolic diseases, such as fatty liver, insulin resistance and type 2 diabetes. Mitochondrial dysfunction and ectopic lipid accumulation in liver are both associated with insulin resistance in human subjects, but the cause and effect nature of these associations remain unclear. Dr. Jurczak’s lab is specifically interested in a mitochondrial repair mechanism called mitophagy that regulates the selective removal of damaged mitochondria via the autophagosomal pathway. Because autophagy is suppressed in mouse models of obesity and fatty liver disease, it is likely that mitophagy is similarly impaired and may contribute to the decline in mitochondrial function seen in human patients. Interestingly, a key component of the mitophagy pathway, a ubiquitin E3 ligase called Parkin, is upregulated in liver of obese mice. This change may represent a compensatory response to remove damaged mitochondria from hepatocytes or result directly from the loss of autophagy. Dr. Jurczak’s group is using a genetic approach to test whether the loss of Parkin-mediated mitophagy in liver predisposes mice to mitochondrial dysfunction, ectopic lipid accumulation and insulin resistance. The lab employs in vivo and ex vivo approaches in transgenic mouse models and specializes in using radioactive and stable metabolic isotopes to measure substrate turnover and flux.