UCP3 expression in liver modulates gene expression and oxidative metabolism in response to fatty acids, and sensitizes mitochondria to permeability transition.
Cell Physiol Biochem
; 24(3-4): 243-52, 2009.
Article
em En
| MEDLINE
| ID: mdl-19710539
ABSTRACT
BACKGROUND/AIMS:
Uncoupling protein-3 (UCP3) is expressed in liver only under conditions of high fatty acid catabolism. However, the specific role of UCP3 in liver mitochondria and overall hepatic function is still poorly known.METHODS:
A model of "in vivo" induction of UCP3 expression in mouse liver mitochondria via a tail-vein injection of a recombinant adenoviral vector was developed. The effects on liver mitochondrial bioenergetics and permeability transition, liver gene expression, and systemic metabolism were then determined.RESULTS:
UCP3 expression in liver did not cause basal, non-specific, uncoupling but led to a stimulation of palmitate-induced state 4 respiration. UCP3 expression in liver also caused an increase in the expression of certain genes involved in lipid catabolism and metabolic response to starvation (e.g. medium chain acyl-CoA-dehydrogenase or peroxisome proliferator-activated receptor-gamma co-activator-1alpha). UCP3 also conferred to liver mitochondria an enhanced sensitivity to classical inducers of permeability transition, such as calcium and carboxyatractylate.CONCLUSION:
UCP3 expression in liver exerts direct actions on mitochondrial activity, favoring fatty acid-induced uncoupling and sensitizing mitochondria to permeability transition, as well as causing retrograde signaling to nuclear gene expression consistent with favoring lipid catabolism and oxidative metabolism.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
/
Proteínas Mitocondriais
/
Ácidos Graxos
/
Canais Iônicos
/
Mitocôndrias Musculares
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Cell Physiol Biochem
Assunto da revista:
BIOQUIMICA
/
FARMACOLOGIA
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Espanha