| Literature DB >> 35508111 |
Dzmitry Mukha1, Mariam Fokra2, Alona Feldman2, Boris Sarvin2, Nikita Sarvin2, Keren Nevo-Dinur2, Elazar Besser2, Elior Hallo2, Elina Aizenshtein2, Zachary T Schug3, Tomer Shlomi4.
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.Entities:
Keywords: GCS; GLDC; PDH; glycine cleavage system; glycine decarboxylase; hepatocellular carcinoma; one-carbon metabolism; protein P; protein lipoylation; pyruvate dehydrogenase
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Year: 2022 PMID： 35508111 PMCID： PMC9583459 DOI： 10.1016/j.cmet.2022.04.006
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 31.373