Phosphatidylethanolamine is an abundant component of most cellular membranes whose physical and chemical properties modulate multiple aspects of organelle membrane dynamics. An evolutionarily ancient mechanism for producing phosphatidylethanolamine is to decarboxylate phosphatidylserine and the enzyme catalyzing this reaction, phosphatidylserine decarboxylase, localizes to the inner membrane of the mitochondrion. We characterize a second form of phosphatidylserine decarboxylase, termed PISD-LD, that is generated by alternative splicing of PISD pre-mRNA and localizes to lipid droplets and to mitochondria. Sub-cellular targeting is controlled by a common segment of PISD-LD that is distinct from the catalytic domain and is regulated by nutritional state. Growth conditions that promote neutral lipid storage in lipid droplets favors targeting to lipid droplets, while targeting to mitochondria is favored by conditions that promote consumption of lipid droplets. Depletion of both forms of phosphatidylserine decarboxylase impairs triacylglycerol synthesis when cells are challenged with free fatty acid, indicating a crucial role phosphatidylserine decarboxylase in neutral lipid storage. The results reveal a previously unappreciated role for phosphatidylserine decarboxylase in lipid droplet biogenesis.

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有条件地将磷脂酰丝氨酸脱羧酶靶向脂质滴

磷脂酰乙醇胺是大多数细胞膜的重要组成部分，其物理和化学性质调节细胞器膜动力学的多个方面。生产磷脂酰乙醇胺的一种进化上古老的机制是使磷脂酰丝氨酸脱羧，而催化该反应的酶磷脂酰丝氨酸脱羧酶定位于线粒体的内膜。我们表征了称为PISD-LD的磷脂酰丝氨酸脱羧酶的第二种形式，它是由PISD pre-mRNA的可变剪接产生的，并且定位于脂质滴和线粒体。亚细胞靶向受PISD-LD的共同部分控制，该部分与催化域不同，并受营养状态调节。促进脂质液滴中性脂质存储的生长条件有利于靶向脂质液滴，而靶向线粒体则受到促进脂质液滴消耗的条件的促进。当细胞受到游离脂肪酸攻击时，两种形式的磷脂酰丝氨酸脱羧酶的消耗都会破坏三酰基甘油的合成，这表明磷脂酰丝氨酸脱羧酶在中性脂质存储中起着至关重要的作用。该结果揭示了磷脂酰丝氨酸脱羧酶在脂质小滴的生物发生中以前没有被认识到的作用。表明磷脂酰丝氨酸脱羧酶在中性脂质储存中起关键作用。结果揭示了磷脂酰丝氨酸脱羧酶在脂质微滴生物发生中的作用，这一点以前未被认识。表明磷脂酰丝氨酸脱羧酶在中性脂质储存中起关键作用。该结果揭示了磷脂酰丝氨酸脱羧酶在脂质小滴的生物发生中以前没有被认识到的作用。