| RRC ID |
59586
|
| 著者 |
Ruiz M, Bodhicharla R, Ståhlman M, Svensk E, Busayavalasa K, Palmgren H, Ruhanen H, Boren J, Pilon M.
|
| タイトル |
Evolutionarily conserved long-chain Acyl-CoA synthetases regulate membrane composition and fluidity.
|
| ジャーナル |
Elife
|
| Abstract |
The human AdipoR1 and AdipoR2 proteins, as well as their C. elegans homolog PAQR-2, protect against cell membrane rigidification by exogenous saturated fatty acids by regulating phospholipid composition. Here, we show that mutations in the C. elegans gene acs-13 help to suppress the phenotypes of paqr-2 mutant worms, including their characteristic membrane fluidity defects. acs-13 encodes a homolog of the human acyl-CoA synthetase ACSL1, and localizes to the mitochondrial membrane where it likely activates long chains fatty acids for import and degradation. Using siRNA combined with lipidomics and membrane fluidity assays (FRAP and Laurdan dye staining) we further show that the human ACSL1 potentiates lipotoxicity by the saturated fatty acid palmitate: silencing ACSL1 protects against the membrane rigidifying effects of palmitate and acts as a suppressor of AdipoR2 knockdown, thus echoing the C. elegans findings. We conclude that acs-13 mutations in C. elegans and ACSL1 knockdown in human cells prevent lipotoxicity by promoting increased levels of polyunsaturated fatty acid-containing phospholipids.
|
| 巻・号 |
8
|
| 公開日 |
2019-11-26
|
| DOI |
10.7554/eLife.47733
|
| PII |
47733
|
| PMID |
31769755
|
| PMC |
PMC6901333
|
| MeSH |
Animals
Caenorhabditis elegans / genetics*
Caenorhabditis elegans / metabolism
Caenorhabditis elegans Proteins / genetics*
Cell Membrane / genetics
Coenzyme A Ligases / genetics*
Coenzyme A Ligases / metabolism
Conserved Sequence / genetics
Evolution, Molecular*
Humans
Membrane Fluidity / genetics
Membrane Proteins / genetics*
Mutation / genetics
Phenotype
RNA, Small Interfering / genetics
Receptors, Adiponectin / genetics
|
| IF |
7.551
|
| 引用数 |
3
|
| リソース情報 |
| 線虫 |
tm3410 |
