Reference - Detail
| RRC ID | 36635 |
|---|---|
| Author | Ranji P, Rauthan M, Pitot C, Pilon M. |
| Title | Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and muscle mitochondria. |
| Journal | PLoS One |
| Abstract |
HMG-CoA reductase is the rate-limiting enzyme in the mevalonate pathway and the target of cholesterol-lowering statins. We characterized the C. elegans hmgr-1(tm4368) mutant, which lacks HMG-CoA reductase, and show that its phenotypes recapitulate that of statin treatment, though in a more severe form. Specifically, the hmgr-1(tm4368) mutant has defects in growth, reproduction and protein prenylation, is rescued by exogenous mevalonate, exhibits constitutive activation of the UPRer and requires less mevalonate to be healthy when the UPRmt is activated by a constitutively active form of ATFS-1. We also show that different amounts of mevalonate are required for different physiological processes, with reproduction requiring the highest levels. Finally, we provide evidence that the mevalonate pathway is required for the activation of the UPRmt. |
| Volume | 9(2) |
| Pages | e100033 |
| Published | 2014-1-1 |
| DOI | 10.1371/journal.pone.0100033 |
| PII | PONE-D-14-05894 |
| PMID | 24918786 |
| PMC | PMC4053411 |
| MeSH | Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Gene Deletion* Hydroxymethylglutaryl CoA Reductases / genetics* Hydroxymethylglutaryl CoA Reductases / metabolism Mevalonic Acid / metabolism Mitochondria, Muscle / genetics Mitochondria, Muscle / pathology Mitochondria, Muscle / ultrastructure* Protein Prenylation* Reproduction Signal Transduction Transcription Factors / metabolism |
| IF | 2.74 |
| Times Cited | 8 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Resource | |
| C.elegans | tm4368 |