Unraveling the 2,3-diketo-L-gulonic acid-dependent and -independent impacts of L-ascorbic acid on somatic cell reprogramming.
Asc
DKG
MET
Metabolite
TCA cycle
Journal
Cell & bioscience
ISSN: 2045-3701
Titre abrégé: Cell Biosci
Pays: England
ID NLM: 101561195
Informations de publication
Date de publication:
30 Nov 2023
30 Nov 2023
Historique:
received:
13
08
2023
accepted:
31
10
2023
medline:
1
12
2023
pubmed:
1
12
2023
entrez:
1
12
2023
Statut:
epublish
Résumé
L-ascorbic acid (Asc) plays a pivotal role in regulating various biological processes, including somatic cell reprogramming, through multiple pathways. However, it remains unclear whether Asc regulates reprogramming directly or functions through its metabolites. Asc exhibited dual capabilities in promoting reprogramming through both 2,3-diketo-L-gulonic acid (DKG), a key metabolite during Asc degradation, dependent and independent routes. On the one hand, Asc facilitated reprogramming by promoting cell proliferation and inducing the conversion from pre-induced pluripotent stem cells (pre-iPSCs) to iPSCs through DKG-independent pathways. Additionally, Asc triggered mesenchymal-epithelial transition (MET) and activated glycolysis via DKG-dependent mechanisms. Notably, DKG alone activated a non-canonical tricarboxylic acid cycle characterized by increased succinate, fumarate, and malate. Consequently, this shift redirected oxidative phosphorylation toward glycolysis and induced MET. Moreover, owing to its antioxidant capabilities, Asc directly inhibited glycolysis, thereby preventing positive feedback between glycolysis and epithelial-mesenchymal transition, ultimately resulting in a higher level of MET. These findings unveil the intricate functions of Asc in the context of reprogramming. This study sheds light on the DKG-dependent and -independent activities of Asc during reprogramming, offering novel insights that may extend the application of Asc to other biological processes.
Sections du résumé
BACKGROUND
BACKGROUND
L-ascorbic acid (Asc) plays a pivotal role in regulating various biological processes, including somatic cell reprogramming, through multiple pathways. However, it remains unclear whether Asc regulates reprogramming directly or functions through its metabolites.
RESULTS
RESULTS
Asc exhibited dual capabilities in promoting reprogramming through both 2,3-diketo-L-gulonic acid (DKG), a key metabolite during Asc degradation, dependent and independent routes. On the one hand, Asc facilitated reprogramming by promoting cell proliferation and inducing the conversion from pre-induced pluripotent stem cells (pre-iPSCs) to iPSCs through DKG-independent pathways. Additionally, Asc triggered mesenchymal-epithelial transition (MET) and activated glycolysis via DKG-dependent mechanisms. Notably, DKG alone activated a non-canonical tricarboxylic acid cycle characterized by increased succinate, fumarate, and malate. Consequently, this shift redirected oxidative phosphorylation toward glycolysis and induced MET. Moreover, owing to its antioxidant capabilities, Asc directly inhibited glycolysis, thereby preventing positive feedback between glycolysis and epithelial-mesenchymal transition, ultimately resulting in a higher level of MET.
CONCLUSION
CONCLUSIONS
These findings unveil the intricate functions of Asc in the context of reprogramming. This study sheds light on the DKG-dependent and -independent activities of Asc during reprogramming, offering novel insights that may extend the application of Asc to other biological processes.
Identifiants
pubmed: 38037169
doi: 10.1186/s13578-023-01160-x
pii: 10.1186/s13578-023-01160-x
pmc: PMC10688016
doi:
Types de publication
Journal Article
Langues
eng
Pagination
218Subventions
Organisme : National Key R&D Program of China
ID : 2021YFA1100401
Organisme : KNational Key R&D Program of China
ID : 2021YFA1101304
Organisme : National Natural Science Foundation of China
ID : U21A20203
Organisme : National Natural Science Foundation of China
ID : 32070717
Organisme : National Natural Science Foundation of China
ID : 32170741
Organisme : National Natural Science Foundation of China
ID : 32100472
Organisme : Science and Technology Program of Guangzhou
ID : 202102020044
Organisme : Science and Technology Program of Guangzhou
ID : 202102020183
Organisme : Science and Technology Program of Guangzhou
ID : 202201011654
Organisme : Science and Technology Planning Project of Guangdong Province
ID : 2020B1212060052
Informations de copyright
© 2023. The Author(s).
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