Glycine decarboxylase maintains mitochondrial protein lipoylation to support tumor growth.
GCS
GLDC
PDH
glycine cleavage system
glycine decarboxylase
hepatocellular carcinoma
one-carbon metabolism
protein P
protein lipoylation
pyruvate dehydrogenase
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
03 05 2022
03 05 2022
Historique:
received:
26
12
2020
revised:
01
12
2021
accepted:
12
04
2022
entrez:
4
5
2022
pubmed:
5
5
2022
medline:
7
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35508111
pii: S1550-4131(22)00133-4
doi: 10.1016/j.cmet.2022.04.006
pmc: PMC9583459
mid: NIHMS1816080
pii:
doi:
Substances chimiques
Mitochondrial Proteins
0
Nucleotides
0
Folic Acid
935E97BOY8
Glycine Dehydrogenase (Decarboxylating)
EC 1.4.4.2
Glycine
TE7660XO1C
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
775-782.e9Subventions
Organisme : NCI NIH HHS
ID : DP2 CA249950
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA114046
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests T.S. is a co-founder and consultant in MetaboMed Ltd.
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