Iershov, Anton, Nemazanyy, Ivan, Alkhoury, Chantal, Girard, Muriel, Barth, Esther, Cagnard, Nicolas, Montagner, Alexandra ORCID: 0000-0002-4800-5105, Chretien, Dominique, Rugarli, Elena I. ORCID: 0000-0002-5782-1067, Guillou, Herve ORCID: 0000-0002-5363-9081, Pende, Mario ORCID: 0000-0002-7864-8937 and Panasyuk, Ganna (2019). The class 3 PI3K coordinates autophagy and mitochondrial lipid catabolism by controlling nuclear receptor PPAR alpha. Nat. Commun., 10. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

Full text not available from this repository.

Abstract

The class 3 phosphoinositide 3-kinase (PI3K) is required for lysosomal degradation by autophagy and vesicular trafficking, assuring nutrient availability. Mitochondrial lipid catabolism is another energy source. Autophagy and mitochondrial metabolism are transcriptionally controlled by nutrient sensing nuclear receptors. However, the class 3 PI3K contribution to this regulation is unknown. We show that liver-specific inactivation of Vps15, the essential regulatory subunit of the class 3 PI3K, elicits mitochondrial depletion and failure to oxidize fatty acids. Mechanistically, transcriptional activity of Peroxisome Proliferator Activated Receptor alpha (PPAR alpha), a nuclear receptor orchestrating lipid catabolism, is blunted in Vps15-deficient livers. We find PPAR alpha repressors Histone Deacetylase 3 (Hdac3) and Nuclear receptor co-repressor 1 (NCoR1) accumulated in Vps15-deficient livers due to defective autophagy. Activation of PPAR alpha or inhibition of Hdac3 restored mitochondrial biogenesis and lipid oxidation in Vps15-deficient hepatocytes. These findings reveal roles for the class 3 PI3K and autophagy in transcriptional coordination of mitochondrial metabolism.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Iershov, AntonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nemazanyy, IvanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alkhoury, ChantalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Girard, MurielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barth, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cagnard, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Montagner, AlexandraUNSPECIFIEDorcid.org/0000-0002-4800-5105UNSPECIFIED
Chretien, DominiqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rugarli, Elena I.UNSPECIFIEDorcid.org/0000-0002-5782-1067UNSPECIFIED
Guillou, HerveUNSPECIFIEDorcid.org/0000-0002-5363-9081UNSPECIFIED
Pende, MarioUNSPECIFIEDorcid.org/0000-0002-7864-8937UNSPECIFIED
Panasyuk, GannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-150975
DOI: 10.1038/s41467-019-09598-9
Journal or Publication Title: Nat. Commun.
Volume: 10
Date: 2019
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
INSULIN-RESISTANCE; FATTY-ACIDS; LIVER; MUSCLE; METABOLISM; GLUCOSE; PROTEIN; PIK3C3/VPS34; TRANSLATION; EICOSANOIDSMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15097

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item