Journal article
The interplay of protein kinase a and Perilipin 5 regulates cardiac lipolysis
Journal of Biological Chemistry, Vol.290(3), pp.1295-1306
2015
Abstract
Defective lipolysis in mice lacking adipose triglyceride lipase provokes severe cardiac steatosis and heart dysfunction, markedly shortening life span. Similarly, cardiac muscle (CM)-specific Plin5 overexpression (CM-Plin5) leads to severe triglyceride (TG) accumulation in cardiomyocytes via impairing TG breakdown. Interestingly, cardiac steatosis due to overexpression of Plin5 is compatible with normal heart function and life span indicating a more moderate impact of Plin5 overexpression on cardiac lipolysis and energy metabolism. We hypothesized that cardiac Plin5 overexpression does not constantly impair cardiac lipolysis. In line with this assumption, TG levels decreased in CM of fasted compared with nonfasted CMPlin5 mice indicating that fasting may lead to a diminished barrier function of Plin5. Recent studies demonstrated that Plin5 is phosphorylated, and activation of adenylyl cyclase leads to phosphorylation of Plin5, suggesting that Plin5 is a substrate for PKA. Furthermore, any significance of Plin5 phosphorylation by PKA in the regulation of TG mobilization from lipid droplets (LDs) is unknown. Here, we show that the lipolytic barrier of Plin5-enriched LDs, either prepared from cardiac tissue of CM-Plin5 mice or Plin5-transfected cells, is abrogated by incubation with PKA. Notably, PKA-induced lipolysis of LDs enriched with Plin5 carrying a single mutation at serine 155 (PlinS155A) of the putative PKA phosphorylation site was substantially impaired revealing a critical role for PKA in Plin5- regulated lipolysis. The strong increase in protein levels of phosphorylated PKA in CM of Plin5 transgenic mice may partially restore fatty acid release from Plin5-enriched LDs, rendering these hearts compatible with normal heart function despite massive steatosis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
Details
- Title
- The interplay of protein kinase a and Perilipin 5 regulates cardiac lipolysis
- Authors
- Nina M Pollak (Author) - University of Graz, AustriaD Jaeger (Author) - University of Graz, AustriaS Kolleritsch (Author) - University of Graz, AustriaR Zimmermann (Author) - University of Graz, AustriaR Zechner (Author) - University of Graz, AustriaA Lass (Author) - University of Graz, AustriaG Haemmerle (Author) - University of Graz, Austria
- Publication details
- Journal of Biological Chemistry, Vol.290(3), pp.1295-1306
- Publisher
- American Society for Biochemistry and Molecular Biology, Inc.
- Date published
- 2015
- DOI
- 10.1074/jbc.M114.604744
- ISSN
- 0021-9258
- Copyright note
- Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc. The published version is reproduced here in accordance with the publisher's copyright policy
- Organisation Unit
- School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99450517802621
- Output Type
- Journal article
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