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Updated: Sep 24, 2025

Evaluation of Amino Acid Consumption in Cultured Bone Cells and Isolated Bone Shafts
Published on: April 13, 2022
Glycine decarboxylase maintains mitochondrial protein lipoylation to support tumor growth
Dzmitry Mukha1, Mariam Fokra2, Alona Feldman2
1Faculty of Biology, Technion - Israel Institute of Technology, Technion City, Haifa 3200003, Israel; The Wistar Institute of Anatomy and Biology, Program in Molecular and Cellular Oncogenesis, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Abstract:
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 GCS is important for maintaining protein lipoylation and mitochondrial activity. Genetic silencing of glycine decarboxylase inhibits the lipoylation and activity of pyruvate dehydrogenase and impairs tumor growth, suggesting a novel drug target for HCC. Considering the physiological role of liver glycine cleavage, our results support the notion that tissue of origin plays an important role in tumor-specific metabolic rewiring.
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