Phosphatidylserine synthesis at membrane contact sites promotes its transport out of the ER
Phosphatidylserine synthesis at membrane contact sites promotes its transport out of the ER
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DOI：
10.1194/jlr.m072959
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发表时间：
2017-03-01
影响因子：
6.5
通讯作者：
Prinz, William A.
中科院分区：
文献类型：
--
作者：
Kannan, Muthukumar;Lahiri, Sujoy;Prinz, William A.
细胞器之间的紧密接触通常称为膜接触位点 (MCS)，是细胞器之间进行脂质交换的区域。在这里，我们确定了细胞促进 MCS 磷脂交换的新机制。先前的研究表明，磷脂酰丝氨酸（PS）合酶活性在内质网（ER）与线粒体接触的部分高度富集。本研究的目的是确定这种富集是否促进 PS 转运出 ER。我们发现，当PS合酶与ER-线粒体接触处的ER中的蛋白质融合时，PS向线粒体的转运比与ER所有部分中的蛋白质融合时更有效。通过增加这些细胞器之间的束缚，可以纠正 PS 向线粒体的低效运输。内质网与内体接触的区域中 PS 的产生同样增强了 PS 向内体的转运。总之，这些发现表明 MCS 的 PS 产生促进 PS 转运出 ER，并表明 MCS 的磷脂产生可能是将脂质引导至特定细胞区室的一般机制。
Close contacts between organelles, often called membrane contact sites (MCSs), are regions where lipids are exchanged between organelles. Here, we identify a novel mechanism by which cells promote phospholipid exchange at MCSs. Previous studies have shown that phosphatidylserine (PS) synthase activity is highly enriched in portions of the endoplasmic reticulum (ER) in contact with mitochondria. The objective of this study was to determine whether this enrichment promotes PS transport out of the ER. We found that PS transport to mitochondria was more efficient when PS synthase was fused to a protein in the ER at ER- mitochondria contacts than when it was fused to a protein in all portions of the ER. Inefficient PS transport to mitochondria was corrected by increasing tethering between these organelles. PS transport to endosomes was similarly enhanced by PS production in regions of the ER in contact with endosomes. Together, these findings indicate that PS production at MCSs promotes PS transport out of the ER and suggest that phospholipid production at MCSs may be a general mechanism of channeling lipids to specific cellular compartments.