Autophagy regulates lipid metabolism through selective turnover of NCoR1.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 04 2019
05 04 2019
Historique:
received:
27
05
2018
accepted:
29
01
2019
entrez:
7
4
2019
pubmed:
7
4
2019
medline:
10
5
2019
Statut:
epublish
Résumé
Selective autophagy ensures the removal of specific soluble proteins, protein aggregates, damaged mitochondria, and invasive bacteria from cells. Defective autophagy has been directly linked to metabolic disorders. However how selective autophagy regulates metabolism remains largely uncharacterized. Here we show that a deficiency in selective autophagy is associated with suppression of lipid oxidation. Hepatic loss of Atg7 or Atg5 significantly impairs the production of ketone bodies upon fasting, due to decreased expression of enzymes involved in β-oxidation following suppression of transactivation by PPARα. Mechanistically, nuclear receptor co-repressor 1 (NCoR1), which interacts with PPARα to suppress its transactivation, binds to the autophagosomal GABARAP family proteins and is degraded by autophagy. Consequently, loss of autophagy causes accumulation of NCoR1, suppressing PPARα activity and resulting in impaired lipid oxidation. These results suggest that autophagy contributes to PPARα activation upon fasting by promoting degradation of NCoR1 and thus regulates β-oxidation and ketone bodies production.
Identifiants
pubmed: 30952864
doi: 10.1038/s41467-019-08829-3
pii: 10.1038/s41467-019-08829-3
pmc: PMC6450892
doi:
Substances chimiques
Atg5 protein, mouse
0
Atg7 protein, mouse
0
Autophagy-Related Protein 5
0
Ketone Bodies
0
Nuclear Receptor Co-Repressor 1
0
PPAR alpha
0
Autophagy-Related Protein 7
EC 6.2.1.45
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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