In macroautophagy, membrane structures called autophagosomes engulf substrates and deliver them for lysosomal degradation. Autophagosomes enwrap a variety of targets with diverse sizes, from portions of cytosol to larger organelles. However, the mechanism by which autophagosome size is controlled remains elusive. We characterized a novel ER membrane protein, ERdj8, in mammalian cells. ERdj8 localizes to a meshwork-like ER subdomain along with phosphatidylinositol synthase (PIS) and autophagy-related (Atg) proteins. ERdj8 overexpression extended the size of the autophagosome through its DnaJ and TRX domains. ERdj8 ablation resulted in a defect in engulfing larger targets. C. elegans, in which the ERdj8 orthologue dnj-8 was knocked down, could perform autophagy on smaller mitochondria derived from the paternal lineage but not the somatic mitochondria. Thus, ERdj8 may play a critical role in autophagosome formation by providing the capacity to target substrates of diverse sizes for degradation.

中文翻译：

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ERdj8 在形成过程中控制自噬体的大小

在巨自噬中，称为自噬体的膜结构吞噬底物并将其输送至溶酶体降解。自噬体包裹着各种大小不同的靶标，从细胞质的一部分到较大的细胞器。然而，控制自噬体大小的机制仍然难以捉摸。我们在哺乳动物细胞中表征了一种新型 ER 膜蛋白 ERdj8。ERdj8 与磷脂酰肌醇合酶 (PIS) 和自噬相关 (Atg) 蛋白一起定位于网状 ER 子结构域。ERdj8 过表达通过其 DnaJ 和 TRX 结构域扩大了自噬体的大小。ERdj8 消融导致吞噬较大目标的缺陷。ERdj8 直系同源物 dnj-8 被敲除的线虫可以对源自父系谱系的较小线粒体进行自噬，但不能对体细胞线粒体进行自噬。因此，ERdj8 可能通过提供不同大小的目标底物降解的能力，在自噬体形成中发挥关键作用。