Phosphatidylserine synthase regulates cellular homeostasis through distinct metabolic mechanisms.,PLOS Genetics

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Phosphatidylserine synthase regulates cellular homeostasis through distinct metabolic mechanisms.
PLOS Genetics ( IF 4.0 ) Pub Date : 2019-12-23 , DOI: 10.1371/journal.pgen.1008548
Xiao Yang _{1,

2,

3} , Jingjing Liang ₁ , Long Ding _{1,

2} , Xia Li ₁ , Sin-Man Lam ₄ , Guanghou Shui ₁ , Mei Ding ₁ , Xun Huang _{1,

2}

Affiliation

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.

中文翻译：

磷脂酰丝氨酸合酶通过独特的代谢机制调节细胞稳态。

磷脂酰丝氨酸合酶（PSS）在内质网（ER）中合成的磷脂酰丝氨酸（PS）通过不同的途径转运至质膜（PM）和线粒体。PS在不同亚细胞位置的体内功能以及不同PS转运途径之间的协调尚不完全清楚。在这里，我们报告果蝇PSS调节细胞生长，脂质存储和线粒体功能。在pss RNAi中，降低的PS会耗尽质膜Akt，从而导致细胞生长缺陷。从磷脂合成到中性脂质合成的代谢转变导致异位脂质积聚；线粒体PS的降低会损害线粒体蛋白的导入和线粒体的完整性。重要的，通过丢失PI4KIIIα减少PS从ER到PM的运输，部分挽救了pss RNAi的线粒体缺陷。总之，我们的结果揭示了不同PS转运途径之间的平衡，并揭示了PSS通过独特的代谢机制调节细胞稳态。

更新日期：2019-12-25

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