Nuclear Perilipin 5 integrates lipid droplet lipolysis with PGC-1α/SIRT1-dependent transcriptional regulation of mitochondrial function

Violeta I. Gallardo-Montejano, Geetu Saxena, Christine M. Kusminski, Chaofeng Yang, John L. McAfee, Lisa Hahner, Kathleen Hoch, William Dubinsky, Vihang A. Narkar, Perry E. Bickel

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Dysfunctional cellular lipid metabolism contributes to common chronic human diseases, including type 2 diabetes, obesity, fatty liver disease and diabetic cardiomyopathy. How cells balance lipid storage and mitochondrial oxidative capacity is poorly understood. Here we identify the lipid droplet protein Perilipin 5 as a catecholamine-triggered interaction partner of PGC-1α. We report that during catecholamine-stimulated lipolysis, Perilipin 5 is phosphorylated by protein kinase A and forms transcriptional complexes with PGC-1α and SIRT1 in the nucleus. Perilipin 5 promotes PGC-1α co-activator function by disinhibiting SIRT1 deacetylase activity. We show by gain-and-loss of function studies in cells that nuclear Perilipin 5 promotes transcription of genes that mediate mitochondrial biogenesis and oxidative function. We propose that Perilipin 5 is an important molecular link that couples the coordinated catecholamine activation of the PKA pathway and of lipid droplet lipolysis with transcriptional regulation to promote efficient fatty acid catabolism and prevent mitochondrial dysfunction.

Original languageEnglish (US)
Article number12723
JournalNature Communications
Volume7
DOIs
StatePublished - Aug 24 2016

Fingerprint

catecholamine
Lipolysis
Catecholamines
lipids
Lipids
catabolism
lipid metabolism
obesity
biological evolution
proteins
fatty acids
Transcription
Medical problems
Cyclic AMP-Dependent Protein Kinases
cells
liver
genes
Liver
Diabetic Cardiomyopathies
Activator Appliances

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Nuclear Perilipin 5 integrates lipid droplet lipolysis with PGC-1α/SIRT1-dependent transcriptional regulation of mitochondrial function. / Gallardo-Montejano, Violeta I.; Saxena, Geetu; Kusminski, Christine M.; Yang, Chaofeng; McAfee, John L.; Hahner, Lisa; Hoch, Kathleen; Dubinsky, William; Narkar, Vihang A.; Bickel, Perry E.

In: Nature Communications, Vol. 7, 12723, 24.08.2016.

Research output: Contribution to journalArticle

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AU - Yang, Chaofeng

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AU - Hahner, Lisa

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