Seipin concentrates distinct neutral lipids via interactions with their acyl chain carboxyl esters.

Seipin concentrates distinct neutral lipids via interactions with their acyl chain carboxyl esters.
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DOI:
10.1083/jcb.202112068
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发表时间:
2022-09-05
期刊:
The Journal of cell biology
影响因子:
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其他
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Renne等人表明,Seipin促进含有三酰甘油或甾醇酯的脂滴的形成。有人提出,羟基残基之间的相互作用的Seipin复杂和中性脂质羧基酯提供了一个一般的机制Seipin介导的LD形成。脂滴(LD)通过储存多种中性脂质(NL),如三酰甘油(TAG)、甾醇酯(SE)和视黄酯(RE),对细胞脂质稳态至关重要。一个正确的装配含TAG的LD在ER需要Seipin,一个保守的蛋白质往往在脂肪营养不良突变。在这里,我们表明,酵母Seipin Sei 1和它的合作伙伴Ldb 16也促进其他NL在LD中的存储。重要的是,Sei 1/Ldb 16的这种作用在进化上是保守的,因为人Seipin的表达恢复了酵母Seipin突变体中正常的含SE LD。如在TAG的情况下,含SE的LD的形成需要人Seipin或酵母Ldb 16中的羟基残基与NL羧基酯之间的相互作用。这些研究结果提供了一个通用的机制Seipin介导的LD形成,并提出了一个模型,如何Seipin区分NLS脂肪族磷脂酰基链的中心膜双层。
Renne et al. show that Seipin promotes the formation of lipid droplets containing either triacylglycerol or steryl esters. It is proposed that interactions between hydroxyl-residues within the Seipin complex and neutral lipid carboxyl esters provide a general mechanism for Seipin-mediated LD formation. Lipid droplets (LDs) are essential for cellular lipid homeostasis by storing diverse neutral lipids (NLs), such as triacylglycerol (TAG), steryl esters (SE), and retinyl esters (RE). A proper assembly of TAG-containing LDs at the ER requires Seipin, a conserved protein often mutated in lipodystrophies. Here, we show that the yeast Seipin Sei1 and its partner Ldb16 also promote the storage of other NL in LDs. Importantly, this role of Sei1/Ldb16 is evolutionarily conserved as expression of human-Seipin restored normal SE-containing LDs in yeast Seipin mutants. As in the case of TAG, the formation of SE-containing LDs requires interactions between hydroxyl-residues in human Seipin or yeast Ldb16 with NL carboxyl esters. These findings provide a universal mechanism for Seipin-mediated LD formation and suggest a model for how Seipin distinguishes NLs from aliphatic phospholipid acyl chains in the center of the membrane bilayer.
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