Abstract
ABSTRACTSelective autophagy of damaged or redundant organelles is an important mechanism for maintaining cell homeostasis. We found previously that endoplasmic reticulum (ER) stress in the yeast Saccharomyces cerevisiae causes massive ER expansion and triggers the formation of large ER whorls. Here, we show that stress-induced ER whorls are selectively taken up into the vacuole, the yeast lysosome, by a process termed ER-phagy. Import into the vacuole does not involve autophagosomes but occurs through invagination of the vacuolar membrane, indicating that ER-phagy is topologically equivalent to microautophagy. Even so, ER-phagy requires neither the core autophagy machinery nor several other proteins specifically implicated in microautophagy. Thus, autophagy of ER whorls represents a distinct type of organelle-selective autophagy. Finally, we provide evidence that ER-phagy degrades excess ER membrane, suggesting that it contributes to cell homeostasis by controlling organelle size.
Highlights
Autophagy is the transport of cytoplasmic constituents into lysosomes
We found previously that endoplasmic reticulum (ER) stress in the yeast Saccharomyces cerevisiae leads to massive ER expansion, which increases the protein folding capacity of the ER (Bernales et al, 2006; Schuck et al, 2009)
When cells were treated with dithiothreitol (DTT) to block disulfide bond formation and induce protein misfolding in the ER, the peripheral ER appeared as long stretches of cortical membrane with prominent cytoplasmic extensions (Fig. 1B, black and white arrows, respectively)
Summary
Autophagy is the transport of cytoplasmic constituents into lysosomes. Cells utilize this versatile process for many purposes, including the non-selective breakdown of cytoplasm during starvation and the selective removal of damaged or redundant organelles. Three principal types of autophagy are currently being distinguished, namely macroautophagy, microautophagy and, in mammals, chaperone-mediated autophagy (Klionsky, 2004). The key characteristic of macroautophagy is the generation of autophagosomes, which are large double-membrane transport vesicles that engulf their cargo as they form. Autophagosomes subsequently fuse with lysosomes and release their contents into the lytic compartment as part of single-membrane autophagic bodies. Many autophagy-related (Atg) proteins have been identified and can be divided into two groups. The wellconserved core autophagy machinery is essential for the assembly of all autophagosomes and, in yeast, comprises fifteen
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