PhD Graduate Seminar- Miriam Fokra
28/08/2023 13:00


Glycine decarboxylase maintains mitochondrial protein lipoylation to support tumor growth

The folic acid cycle mediates the transfer of one-carbon (1C) units to support nucleotide biosynthesis. While the importance of serine as a mitochondrial and cytosolic donor of folate-mediated 1C units in cancer cells has been thoroughly investigated, a potential role of glycine oxidation remains unclear. We developed an approach for quantifying mitochondrial glycine cleavage system (GCS) flux by combining stable and radioactive isotope tracing with computational flux decomposition. We find high GCS flux in hepatocellular carcinoma (HCC), supporting nucleotide biosynthesis. Surprisingly, other than supplying 1C units, we found that proper function of GCS is important for maintaining protein lipoylation and mitochondrial activity. Genetic silencing of glycine decarboxylase (GLDC) inhibits the lipoylation and activity of pyruvate dehydrogenase (PDH) and impairs tumor growth, suggesting a novel drug target for HCC.