期刊
DEVELOPMENTAL CELL
卷 44, 期 2, 页码 261-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2017.11.023
关键词
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资金
- NIH [R01 GM106019, R37 GM097432, K99 HL133372, P50 GM102706]
- NIDDK
- Center for RNA Systems Biology
- HHMI
- Damon Runyon Cancer Research Foundation [DRG-2085-11]
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.
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