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- Title
Loss of HMG-CoA Reductase in <i>C. elegans</i> Causes Defects in Protein Prenylation and Muscle Mitochondria.
- Authors
Ranji, Parmida; Rauthan, Manish; Pitot, Christophe; Pilon, Marc
- 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.
- Subjects
ISOPRENYLATION; MUSCLE mitochondria; REDUCTASES; MEVALONATE kinase; ANTICHOLESTEREMIC agents; STATINS (Cardiovascular agents)
- Publication
PLoS ONE, 2014, Vol 9, Issue 6, p1
- ISSN
1932-6203
- Publication type
Academic Journal
- DOI
10.1371/journal.pone.0100033