Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and muscle mitochondria.
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 fo...
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doaj-7d59a3acdccf4e4fb36f763e3745c8bd2020-11-24T21:32:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e10003310.1371/journal.pone.0100033Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and muscle mitochondria.Parmida RanjiManish RauthanChristophe PitotMarc PilonHMG-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.http://europepmc.org/articles/PMC4053411?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Parmida Ranji Manish Rauthan Christophe Pitot Marc Pilon |
spellingShingle |
Parmida Ranji Manish Rauthan Christophe Pitot Marc Pilon Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and muscle mitochondria. PLoS ONE |
author_facet |
Parmida Ranji Manish Rauthan Christophe Pitot Marc Pilon |
author_sort |
Parmida Ranji |
title |
Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and muscle mitochondria. |
title_short |
Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and muscle mitochondria. |
title_full |
Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and muscle mitochondria. |
title_fullStr |
Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and muscle mitochondria. |
title_full_unstemmed |
Loss of HMG-CoA reductase in C. elegans causes defects in protein prenylation and muscle mitochondria. |
title_sort |
loss of hmg-coa reductase in c. elegans causes defects in protein prenylation and muscle mitochondria. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4053411?pdf=render |
work_keys_str_mv |
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