The autophagy protein ATG2, proposed to transfer bulk lipid from the endoplasmic reticulum (ER) during autophagosome biogenesis, interacts with ER residents TMEM41B and VMP1 and with ATG9, in Golgi-derived vesicles that initiate autophagosome formation. In vitro assays reveal TMEM41B, VMP1, and ATG9 as scramblases. We propose a model wherein membrane expansion results from the partnership of a lipid transfer protein, moving lipids between the cytosolic leaflets of apposed organelles, and scramblases that reequilibrate the leaflets of donor and acceptor organelle membranes as lipids are depleted or augmented. TMEM41B and VMP1 are implicated broadly in lipid homeostasis and membrane dynamics processes in which their scrambling activities likely are key.

自噬蛋白 ATG2 被提议在自噬体生物发生过程中从内质网 (ER) 转移大量脂质，它与 ER 居民 TMEM41B 和 VMP1 以及与高尔基体衍生的囊泡中的 ATG9 相互作用，从而启动自噬体的形成。体外测定显示 TMEM41B、VMP1 和 ATG9 是加扰酶。我们提出了一个模型，其中膜扩张是由脂质转移蛋白的合作产生的，在并列细胞器的细胞溶质小叶之间移动脂质，以及在脂质耗尽或增加时重新平衡供体和受体细胞器膜的小叶的加扰酶。TMEM41B 和 VMP1 广泛参与脂质稳态和膜动力学过程，其中它们的加扰活动可能是关键。