The EMBO Journal
Abstract
Seipin, the gene that causes Berardinelli‐Seip congenital lipodystrophy type 2 (BSCL2), is important for adipocyte differentiation and lipid homeostasis. Previous studies inDrosophilarevealed that Seipin promotesERcalcium homeostasis through the Ca2+‐ATPaseSERCA, but little is known about the events downstream of perturbedERcalcium homeostasis that lead to decreased lipid storage inDrosophiladSeipinmutants. Here, we show that glycolytic metabolites accumulate and the downstream mitochondrialTCAcycle is impaired indSeipinmutants. The impairedTCAcycle further leads to a decreased level of citrate, a critical component of lipogenesis. Mechanistically, Seipin/SERCA‐mediatedERcalcium homeostasis is important for maintaining mitochondrial calcium homeostasis. Reduced mitochondrial calcium indSeipinmutants affects theTCAcycle and mitochondrial function. The lipid storage defects indSeipinmutant 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.
| 论文编号: | DOI:10.15252/embj.201797572 |
| 论文题目: | Seipin Regulates Lipid Homeostasis by Ensuring Calcium‐Dependent Mitochondrial Metabolism |
| 英文论文题目: | Seipin Regulates Lipid Homeostasis by Ensuring Calcium‐Dependent Mitochondrial Metabolism |
| 第一作者: | Long Ding, XiaoYang, HeTian, Jingjing Liang, Fengxia Zhang, Guodong Wang, Yingchun Wang, Mei Ding, Guanghou Shui, Xun Huang |
| 英文第一作者: | Long Ding, XiaoYang, HeTian, Jingjing Liang, Fengxia Zhang, Guodong Wang, Yingchun Wang, Mei Ding, Guanghou Shui, Xun Huang |
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| 发表年度: | 2018-07-30 |
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| 摘要: | Seipin, the gene that causes Berardinelli‐Seip congenital lipodystrophy type 2 (BSCL2), is important for adipocyte differentiation and lipid homeostasis. Previous studies inDrosophilarevealed that Seipin promotesERcalcium homeostasis through the Ca2+‐ATPaseSERCA, but little is known about the events downstream of perturbedERcalcium homeostasis that lead to decreased lipid storage inDrosophiladSeipinmutants. Here, we show that glycolytic metabolites accumulate and the downstream mitochondrialTCAcycle is impaired indSeipinmutants. The impairedTCAcycle further leads to a decreased level of citrate, a critical component of lipogenesis. Mechanistically, Seipin/SERCA‐mediatedERcalcium homeostasis is important for maintaining mitochondrial calcium homeostasis. Reduced mitochondrial calcium indSeipinmutants affects theTCAcycle and mitochondrial function. The lipid storage defects indSeipinmutant 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. |
| 英文摘要: | Seipin, the gene that causes Berardinelli‐Seip congenital lipodystrophy type 2 (BSCL2), is important for adipocyte differentiation and lipid homeostasis. Previous studies inDrosophilarevealed that Seipin promotesERcalcium homeostasis through the Ca2+‐ATPaseSERCA, but little is known about the events downstream of perturbedERcalcium homeostasis that lead to decreased lipid storage inDrosophiladSeipinmutants. Here, we show that glycolytic metabolites accumulate and the downstream mitochondrialTCAcycle is impaired indSeipinmutants. The impairedTCAcycle further leads to a decreased level of citrate, a critical component of lipogenesis. Mechanistically, Seipin/SERCA‐mediatedERcalcium homeostasis is important for maintaining mitochondrial calcium homeostasis. Reduced mitochondrial calcium indSeipinmutants affects theTCAcycle and mitochondrial function. The lipid storage defects indSeipinmutant 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. |
| 刊物名称: | The EMBO Journal |
| 英文刊物名称: | The EMBO Journal |
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| 其它备注: | Long Ding, XiaoYang, HeTian, Jingjing Liang, Fengxia Zhang, Guodong Wang, Yingchun Wang, Mei Ding, Guanghou Shui, Xun Huang. Seipin Regulates Lipid Homeostasis by Ensuring Calcium‐Dependent Mitochondrial Metabolism. The EMBO Journal. DOI:10.15252/embj.201797572 |
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