Bernales Sebastián, Schuck Sebastian, Walter Peter
Howard Hughes Medical Institute, Department of Biochemistry, School of Medicine, University of California San Francisco, San Francisco, California 94158-2517, USA.
Autophagy. 2007 May-Jun;3(3):285-7. doi: 10.4161/auto.3930. Epub 2007 May 1.
Throughout their life, cells must maintain homeostasis while facing constantly fluctuating demands on their different organelles. A major mechanism for the homeostatic control of organelle function is the unfolded protein response (UPR), a signaling pathway that triggers a comprehensive remodeling of the endoplasmic reticulum (ER) and the biosynthetic pathway according to need. We discovered that activation of the UPR in yeast also induces a new branch of macroautophagy that selectively targets the ER. We term this process "ER-phagy", in analogy to pexophagy and mitophagy, the two other known forms of organelle-specific marcoautophagy. ER-phagy involves the generation of autophagosomes that selectively include ER membranes and whose delimiting double membranes also derive, at least in part, from the ER. This finding provides direct evidence that the ER can serve as a membrane source for autophagosome formation and indicates that ER-phagy entails engulfment of the ER by itself. ER-phagy could remove damaged or redundant parts of the ER and thus represent an important degradative functionality of the UPR that helps to afford homeostatic control.
在整个生命过程中,细胞必须维持内稳态,同时还要应对对其不同细胞器不断变化的需求。细胞器功能稳态控制的一个主要机制是未折叠蛋白反应(UPR),这是一种信号通路,可根据需要触发内质网(ER)和生物合成途径的全面重塑。我们发现,酵母中UPR的激活还会诱导一种新的巨自噬分支,该分支选择性地靶向内质网。我们将此过程称为“内质网自噬”,类似于过氧化物酶体自噬和线粒体自噬,这是另外两种已知的细胞器特异性巨自噬形式。内质网自噬涉及自噬体的产生,这些自噬体选择性地包含内质网膜,其界定双层膜至少部分也源自内质网。这一发现提供了直接证据,表明内质网可作为自噬体形成的膜来源,并表明内质网自噬需要内质网自身的吞噬作用。内质网自噬可以去除内质网受损或多余的部分,因此代表了未折叠蛋白反应的一种重要降解功能,有助于实现稳态控制。