Phosphatidylserine synthetase regulates cellular homeostasis through distinct metabolic mechanisms

English version

Autoři: Xiao Yang ^aff001; Jingjing Liang ^aff001; Long Ding ^aff001; Xia Li ^aff001; Sin-Man Lam ^aff004; Guanghou Shui ^aff001; Mei Ding ^aff001; Xun Huang ^aff001
Působiště autorů: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China ^aff001; University of Chinese Academy of Sciences, Beijing, China ^aff002; School of Life Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, TaiAn, China ^aff003; LipidAll Technologies Co., Ltd. Changzhou, China ^aff004
Vyšlo v časopise: Phosphatidylserine synthetase regulates cellular homeostasis through distinct metabolic mechanisms. PLoS Genet 15(12): e1008548. doi:10.1371/journal.pgen.1008548
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008548

Souhrn

Phosphatidylserine (PS), synthesized in the endoplasmic reticulum (ER) by phosphatidylserine synthetase (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.

Klíčová slova:

Cell growth – Cell membranes – Drosophila melanogaster – Lipids – Mitochondria – RNA interference – Salivary glands – Hormone transport

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