Summary of project PR000333

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000333. The data can be accessed directly via it's Project DOI: 10.21228/M88885 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR000333
Project DOI:doi: 10.21228/M88885
Project Title:The ubiquitin ligase MuRF1 regulates PPARα activity in the heart by enhancing nuclear export via monoubiquitination
Project Type:Targeted Metabolomics
Project Summary:The transcriptional regulation of peroxisome proliferator-activated receptor (PPAR) α by post-translational modification, such as ubiquitin, has not been described. We report here for the first time an ubiquitin ligase (muscle ring finger-1/MuRF1) that inhibits fatty acid oxidation by inhibiting PPARα, but not PPARβ/δ or PPARγ in cardiomyocytes in vitro. Similarly, MuRF1 Tg+ hearts showed significant decreases in nuclear PPARα activity and acyl-carnitine intermediates, while MuRF1−/− hearts exhibited increased PPARα activity and acyl-carnitine intermediates. MuRF1 directly interacts with PPARα, mono-ubiquitinates it, and targets it for nuclear export to inhibit fatty acid oxidation in a proteasome independent manner. We then identified a previously undescribed nuclear export sequence in PPARα, along with three specific lysines (292, 310, 388) required for MuRF1's targeting of nuclear export. These studies identify the role of ubiquitination in regulating cardiac PPARα, including the ubiquitin ligase that may be responsible for this critical regulation of cardiac metabolism in heart failure.
Institute:University of North Carolina at Chapel Hill
Department:McAllister Heart Institute, Department of Internal Medicine
Laboratory:Multiple Centers
Last Name:Willis
First Name:Monte
Address:111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Email:monte_willis@med.unc.edu
Phone:919-360-7599
Funding Source:NIH, Fondation Leducq, AHA mid-Atlantic affiliate, AHA scientist development grant, Jefferson-Pilot Corporation Fellowship in Academic Medicine

Summary of all studies in project PR000333

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
Release
Date
VersionSamplesDownload
(* : Contains raw data)
ST000429 Targeted metabolomics of MuRF1 overexpressing cardiomyocytes compared to their wildtype controls (part I) Mus musculus University of North Carolina at Chapel Hill MS 2016-09-23 1 6 Not available
ST000430 Targeted metabolomics of MuRF1 Knockdown cardiomyocytes compared to their wildtype controls (part II) Mus musculus University of North Carolina at Chapel Hill MS 2016-09-23 1 8 Not available
  logo