Link: University of Iowa

Sean Tompkins (Taylor Lab) publishes thesis in Cell Reports

Sean Tompkins, a MSTP student in Dr. Eric Taylor’s lab, had his thesis published by Cell Reports. His thesis is entitled, “Disrupting Mitochondrial Pyruvate Uptake Directs Glutamine into the TCA Cycle away from Glutathione Synthesis and Impairs Hepatocellular Tumorigenesis.”

“Non-alcoholic fatty liver disease (NAFLD) driven by obesity and diabetes is the fastest growing cause of liver cancer in the developed world and new therapies are needed to curb its growing burden. This manuscript demonstrates and helps explain how impairing the ability of liver mitochondria to use a glucose byproduct called pyruvate decreases liver tumor development. Using a mouse model of liver cancer, Tompkins et al. and Taylor discovered that liver-specific disruption of the mitochondrial pyruvate carrier (MPC), the protein complex that transports pyruvate into mitochondria, led to two thirds fewer tumors that were smaller and had a higher cell death rate. Using RNA-sequencing and biochemical assays, they determined that MPC-deficient tumors had impaired glutathione metabolism. Continued experiments using stable isotope tracing and metabolomic analysis demonstrated hepatocyte MPC disruption increases mitochondrial glutamine utilization at the expense of glutathione synthesis, which is critical for tumor development. These results identify modulation of mitochondrial pyruvate uptake as a potential strategy to prevent obesity- and diabetes-driven liver cancer development.”


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