Title :

Citrin deficiency: Does the reactivation of liver aralar-1 come into play and promote HCC development?

Author(s) :

Mention, Karine [Auteur]
Hôpital Jeanne de Flandre [Lille]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Joncquel, Marie [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Dessein, Anne-Frédérique [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP]
Douillard, Claire [Auteur]
Hôpital Jeanne de Flandres
Service Endocrinologie, diabétologie, maladies métaboliques et nutrition [LILLE - Endocrino]
Dobbelaere, Dries [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]
Vamecq, Joseph [Auteur]
Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 [RADEME]

Journal title :

Biochimie

Publisher :

Elsevier

Publication date :

2021-07-12

ISSN :

0300-9084

English keyword(s) :

Hepatocellular carcinoma
Citrin deficiency
Gene re-activation
Gene redundancy
Histone acetylation
Cytosolic NADH redox State
Citrate-malate shuttle
Malate-aspartate shuttle
Aralar-1
Citrin
SLC25A13
SLC25A12
SLC25A1
Mitochondrial solute carriers

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Hepatocellular carcinoma (HCC) is a longstanding issue in clinical practice and metabolic research. New clues in better understanding the pathogenesis of HCC might relate to the metabolic context in patients with citrin ...
Show more >Hepatocellular carcinoma (HCC) is a longstanding issue in clinical practice and metabolic research. New clues in better understanding the pathogenesis of HCC might relate to the metabolic context in patients with citrin (aspartate-glutamate carrier 1) deficiency (CD). Because citrin-deficient liver (CDL) is subject to HCC, it represents a unique metabolic model to highlight the mechanisms of HCC promotion, offering different angles of study than the classical metabolic syndrome/obesity/non-alcoholic fatty liver disease (NAFLD)/HCC study axis. In turn, the metabolic features of HCC could shed light on the pathogenesis of CDL. Among these, HCC-induced re-activation of aralar-1 (aspartate-glutamate carrier 2), physiologically not expressed in the adult liver, might take place in CDL, so gene redundancy for mitochondrial aspartate-glutamate carriers would be exploited by the CDL. This proposed (aralar-1 re-activation) and known (citrate/malate cycle) adaptive mechanisms may substitute for the impaired function in CD and are consistent with the clinical remission stage of CD and CD improvement by medium-chain triglycerides (MCT). However, these metabolic adaptive benefits could also promote HCC development. In CD, as a result of PPARα down-regulation, liver mitochondrial fatty acid-derived acetyl-CoA would, like glucose-derived acetyl-CoA, be used for lipid anabolism and fuel nuclear acetylation events which might trigger aralar-1 re-activation as seen in non-CD HCC. A brief account of these metabolic events which might lead to aralar-1 re-activation in CDL is here given. Consistency of this account for CDL events further relies on the protective roles of PPARα and inhibition of mitochondrial and plasma membrane citrate transporters in non-CD HCC.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Miniaturisation pour la Synthèse, l'Analyse et la Protéomique (MSAP) - USR 3290

Source :

Harvested from HAL