The Pleiotropic Effects of Fumarate: From Mitochondrial Respiration to Epigenetic Rewiring and DNA Repair Mechanisms.
DNA repair
epigenetics
fumarate
metabolism
methylation
Journal
Metabolites
ISSN: 2218-1989
Titre abrégé: Metabolites
Pays: Switzerland
ID NLM: 101578790
Informations de publication
Date de publication:
24 Jul 2023
24 Jul 2023
Historique:
received:
26
06
2023
revised:
18
07
2023
accepted:
21
07
2023
medline:
29
7
2023
pubmed:
29
7
2023
entrez:
29
7
2023
Statut:
epublish
Résumé
Tumor onset and its progression are strictly linked to its metabolic rewiring on the basis of the Warburg effect. In this context, fumarate emerged as a putative oncometabolite mediating cancer progression. Fumarate accumulation is usually driven by fumarate hydratase (FH) loss of function, the enzyme responsible for the reversible conversion of fumarate into malate. Fumarate accumulation acts as a double edge sword: on one hand it takes part in the metabolic rewiring of cancer cells, while on the other it also plays a crucial role in chromatin architecture reorganization. The latter is achieved by competing with a-ketoglutarate-dependent enzymes, eventually altering the cellular methylome profile, which in turn leads to its transcriptome modeling. Furthermore, in recent years, it has emerged that FH has an ability to recruit DNA double strand breaks. The accumulation of fumarate into damaged sites might also determine the DNA repair pathway in charge for the seizure of the lesion, eventually affecting the mutational state of the cells. In this work, we aimed to review the current knowledge on the role of fumarate as an oncometabolite orchestrating the cellular epigenetic landscape and DNA repair machinery.
Identifiants
pubmed: 37512586
pii: metabo13070880
doi: 10.3390/metabo13070880
pmc: PMC10384640
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
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