| RRC ID |
53873
|
| Author |
Ding L, Yang X, Tian H, Liang J, Zhang F, Wang G, Wang Y, Ding M, Shui G, Huang X.
|
| Title |
Seipin regulates lipid homeostasis by ensuring calcium-dependent mitochondrial metabolism.
|
| Journal |
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.
|
| Volume |
37(17)
|
| Published |
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
|
| Times Cited |
10
|
| Resource |
| Drosophila |
|
