The mitochondrial carrier Citrin plays a role in regulating cellular energy during carcinogenesis.
Carbohydrates
/ genetics
Carcinogenesis
/ genetics
Citrullinemia
/ genetics
Cytosol
/ metabolism
Gene Expression Regulation, Neoplastic
/ genetics
Germ-Line Mutation
/ genetics
Glutamates
/ pharmacology
Glutamic Acid
/ analogs & derivatives
Glycolysis
/ genetics
Humans
Mitochondria
/ genetics
Mitochondrial Membrane Transport Proteins
/ antagonists & inhibitors
Molecular Targeted Therapy
Neoplasms
/ drug therapy
Oxidative Phosphorylation
/ drug effects
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
26
08
2018
accepted:
21
05
2019
revised:
16
05
2019
pubmed:
30
8
2019
medline:
21
4
2020
entrez:
30
8
2019
Statut:
ppublish
Résumé
Citrin, encoded by SLC25A13 gene, is an inner mitochondrial transporter that is part of the malate-aspartate shuttle, which regulates the NAD+/NADH ratio between the cytosol and mitochondria. Citrullinemia type II (CTLN-II) is an inherited disorder caused by germline mutations in SLC25A13, manifesting clinically in growth failure that can be alleviated by dietary restriction of carbohydrates. The association of citrin with glycolysis and NAD+/NADH ratio led us to hypothesize that it may play a role in carcinogenesis. Indeed, we find that citrin is upregulated in multiple cancer types and is essential for supplementing NAD+ for glycolysis and NADH for oxidative phosphorylation. Consequently, citrin deficiency associates with autophagy, whereas its overexpression in cancer cells increases energy production and cancer invasion. Furthermore, based on the human deleterious mutations in citrin, we found a potential inhibitor of citrin that restricts cancerous phenotypes in cells. Collectively, our findings suggest that targeting citrin may be of benefit for cancer therapy.
Identifiants
pubmed: 31462712
doi: 10.1038/s41388-019-0976-2
pii: 10.1038/s41388-019-0976-2
doi:
Substances chimiques
Carbohydrates
0
Glutamates
0
Mitochondrial Membrane Transport Proteins
0
SLC25A13 protein, human
0
gamma-benzyl ester glutamic acid
0
Glutamic Acid
3KX376GY7L
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
164-175Références
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