Phosphatidylserine synthase regulates cellular homeostasis through distinct metabolic mechanisms
Phosphatidylserine (PS), synthesized in the endoplasmic reticulum (ER) by phosphatidylserine synthase (PSS), is transported to the plasma membrane (PM) and mitochondria through distinct routes. The in vivo functions of PS at different subcellular locations and the coordination between different PS transport routes are not fully understood. Here, we report that Drosophila PSS regulates cell growth, lipid storage and mitochondrial function. In pss RNAi, reduced PS depletes plasma membrane Akt, contributing to cell growth defects; the metabolic shift from phospholipid synthesis to neutral lipid synthesis results in ectopic lipid accumulation; and the reduction of mitochondrial PS impairs mitochondrial protein import and mitochondrial integrity. Importantly, reducing PS transport from the ER to PM by loss of PI4KIIIα partially rescues the mitochondrial defects of pss RNAi. Together, our results uncover a balance between different PS transport routes and reveal that PSS regulates cellular homeostasis through distinct metabolic mechanisms.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2019 |
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Erschienen: |
2019 |
Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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Enthalten in: |
PLoS genetics - 15(2019), 12 vom: 23. Dez., Seite e1008548 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Yang, Xiao [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 03.03.2020 Date Revised 08.05.2020 published: Electronic-eCollection Citation Status MEDLINE |
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doi: |
10.1371/journal.pgen.1008548 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM304695866 |
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520 | |a Phosphatidylserine (PS), synthesized in the endoplasmic reticulum (ER) by phosphatidylserine synthase (PSS), is transported to the plasma membrane (PM) and mitochondria through distinct routes. The in vivo functions of PS at different subcellular locations and the coordination between different PS transport routes are not fully understood. Here, we report that Drosophila PSS regulates cell growth, lipid storage and mitochondrial function. In pss RNAi, reduced PS depletes plasma membrane Akt, contributing to cell growth defects; the metabolic shift from phospholipid synthesis to neutral lipid synthesis results in ectopic lipid accumulation; and the reduction of mitochondrial PS impairs mitochondrial protein import and mitochondrial integrity. Importantly, reducing PS transport from the ER to PM by loss of PI4KIIIα partially rescues the mitochondrial defects of pss RNAi. Together, our results uncover a balance between different PS transport routes and reveal that PSS regulates cellular homeostasis through distinct metabolic mechanisms | ||
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700 | 1 | |a Ding, Long |e verfasserin |4 aut | |
700 | 1 | |a Li, Xia |e verfasserin |4 aut | |
700 | 1 | |a Lam, Sin-Man |e verfasserin |4 aut | |
700 | 1 | |a Shui, Guanghou |e verfasserin |4 aut | |
700 | 1 | |a Ding, Mei |e verfasserin |4 aut | |
700 | 1 | |a Huang, Xun |e verfasserin |4 aut | |
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