Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 49, Pages 19678-19682Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1117835108
Keywords
heart; metabolism; peroxisome proliferator-activated receptor-gamma coactivator-1 alpha
Categories
Funding
- National Institutes of Health (NIH) [5P01AI070167, HHSN272200700038C, DK062434, HL105278]
- Helmsley Charitable Trust
- European Molecular Biology Organization
- Swiss National Science Foundation
- Salk Center for Nutritional Genomics
Ask authors/readers for more resources
Deficiencies of subunits of the transcriptional regulatory complex Mediator generally result in embryonic lethality, precluding study of its physiological function. Here we describe a missense mutation in Med30 causing progressive cardiomyopathy in homozygous mice that, although viable during lactation, show precipitous lethality 2-3 wk afterweaning. Expression profiling reveals pleiotropic changes in transcription of cardiac genes required for oxidative phosphorylation and mitochondrial integrity. Weaning mice to a ketogenic diet extends viability to 8.5 wk. Thus, we establish a mechanistic connection between Mediator and induction of a metabolic program for oxidative phosphorylation and fatty acid oxidation, in which lethal cardiomyopathy is mitigated by dietary intervention.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available