論文 - 詳細
| RRC ID | 53873 |
|---|---|
| 著者 | Ding L, Yang X, Tian H, Liang J, Zhang F, Wang G, Wang Y, Ding M, Shui G, Huang X. |
| タイトル | Seipin regulates lipid homeostasis by ensuring calcium-dependent mitochondrial metabolism. |
| ジャーナル | EMBO J |
| Abstract |
Seipin, the gene that causes Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), is important for adipocyte differentiation and lipid homeostasis. Previous studies in Drosophila revealed that Seipin promotes ER calcium homeostasis through the Ca2+-ATPase SERCA, but little is known about the events downstream of perturbed ER calcium homeostasis that lead to decreased lipid storage in Drosophila dSeipin mutants. Here, we show that glycolytic metabolites accumulate and the downstream mitochondrial TCA cycle is impaired in dSeipin mutants. The impaired TCA cycle further leads to a decreased level of citrate, a critical component of lipogenesis. Mechanistically, Seipin/SERCA-mediated ER calcium homeostasis is important for maintaining mitochondrial calcium homeostasis. Reduced mitochondrial calcium in dSeipin mutants affects the TCA cycle and mitochondrial function. The lipid storage defects in dSeipin mutant fat cells can be rescued by replenishing mitochondrial calcium or by restoring the level of citrate through genetic manipulations or supplementation with exogenous metabolites. Together, our results reveal that Seipin promotes adipose tissue lipid storage via calcium-dependent mitochondrial metabolism. |
| 巻・号 | 37(17) |
| 公開日 | 2018-9-3 |
| DOI | 10.15252/embj.201797572 |
| PII | embj.201797572 |
| PMID | 30049710 |
| PMC | PMC6120665 |
| MeSH | Adipose Tissue / metabolism Animals Calcium / metabolism* Citric Acid Cycle* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster GTP-Binding Protein gamma Subunits / genetics GTP-Binding Protein gamma Subunits / metabolism* Lipid Metabolism* Mitochondria / genetics Mitochondria / metabolism* Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism |
| IF | 9.889 |
| 引用数 | 10 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 19 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | |