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 ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : 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 |
