Autophagy, a conserved eukaryotic intracellular catabolic pathway, maintains cell homeostasis by lysosomal degradation of cytosolic material engulfed in double membrane vesicles termed autophagosomes, which form upon sealing of single-membrane cisternae called phagophores. While the role of phosphatidylinositol 3-phosphate (PI3P) and phosphatidylethanolamine (PE) in autophagosome biogenesis is well-studied, the roles of other phospholipids in autophagy remain rather obscure. Here we utilized budding yeast to study the contribution of phosphatidylcholine (PC) to autophagy. We reveal for the first time that genetic loss of PC biosynthesis via the CDP-DAG pathway leads to changes in lipid composition of autophagic membranes, specifically replacement of PC by phosphatidylserine (PS). This impairs closure of the autophagic membrane and autophagic flux. Consequently, we show that choline-dependent recovery of de novo PC biosynthesis via the CDP-choline pathway restores autophagosome formation and autophagic flux in PC-deficient cells. Our findings therefore implicate phospholipid metabolism in autophagosome biogenesis.

中文翻译：

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磷脂失衡会损害自噬体的完成

自噬是一种保守的真核细胞内分解代谢途径，通过吞噬双膜囊泡（称为自噬体）的胞质物质的溶酶体降解来维持细胞稳态，双膜囊泡在称为吞噬泡的单膜池密封时形成。虽然磷脂酰肌醇 3-磷酸 (PI3P) 和磷脂酰乙醇胺 (PE) 在自噬体生物发生中的作用已得到充分研究，但其他磷脂在自噬中的作用仍然相当模糊。在这里，我们利用出芽酵母来研究磷脂酰胆碱 (PC) 对自噬的贡献。我们首次揭示了通过 CDP-DAG 途径进行的 PC 生物合成的遗传损失会导致自噬膜脂质成分发生变化，特别是磷脂酰丝氨酸 (PS) 取代 PC。这会损害自噬膜的闭合和自噬通量。通过 CDP-胆碱途径从头开始 PC 生物合成可恢复 PC 缺陷细胞中的自噬体形成和自噬通量。因此，我们的研究结果表明自噬体生物发生中的磷脂代谢。