Developmental Cell
Volume 44, Issue 2, 22 January 2018, Pages 261-270.e6
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Short Article
Lipid Homeostasis Is Maintained by Dual Targeting of the Mitochondrial PE Biosynthesis Enzyme to the ER

https://doi.org/10.1016/j.devcel.2017.11.023Get rights and content
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Highlights

  • Mitochondrial phosphatidylserine decarboxylase Psd1 is also targeted to the ER

  • PE generated by Psd1 at the ER and mitochondria are functionally distinct

  • The organellar localization of Psd1 is modulated based on cellular metabolic needs

Summary

Spatial organization of phospholipid synthesis in eukaryotes is critical for cellular homeostasis. The synthesis of phosphatidylcholine (PC), the most abundant cellular phospholipid, occurs redundantly via the ER-localized Kennedy pathway and a pathway that traverses the ER and mitochondria via membrane contact sites. The basis of the ER-mitochondrial PC synthesis pathway is the exclusive mitochondrial localization of a key pathway enzyme, phosphatidylserine decarboxylase Psd1, which generates phosphatidylethanolamine (PE). We find that Psd1 is localized to both mitochondria and the ER. Our data indicate that Psd1-dependent PE made at mitochondria and the ER has separable cellular functions. In addition, the relative organellar localization of Psd1 is dynamically modulated based on metabolic needs. These data reveal a critical role for ER-localized Psd1 in cellular phospholipid homeostasis, question the significance of an ER-mitochondrial PC synthesis pathway to cellular phospholipid homeostasis, and establish the importance of fine spatial regulation of lipid biosynthesis for cellular functions.

Keywords

phospholipid biosynthesis
phosphatidylserine decarboxylase
ER
mitochondria
lipid transport
ER-mitochondria contacts

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