Article

Membrane expansion alleviates endoplasmic reticulum stress independently of the unfolded protein response

Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
The Journal of Cell Biology (Impact Factor: 9.69). 11/2009; 187(4):525-36. DOI: 10.1083/jcb.200907074
Source: PubMed

ABSTRACT Cells constantly adjust the sizes and shapes of their organelles according to need. In this study, we examine endoplasmic reticulum (ER) membrane expansion during the unfolded protein response (UPR) in the yeast Saccharomyces cerevisiae. We find that membrane expansion occurs through the generation of ER sheets, requires UPR signaling, and is driven by lipid biosynthesis. Uncoupling ER size control and the UPR reveals that membrane expansion alleviates ER stress independently of an increase in ER chaperone levels. Converting the sheets of the expanded ER into tubules by reticulon overexpression does not affect the ability of cells to cope with ER stress, showing that ER size rather than shape is the key factor. Thus, increasing ER size through membrane synthesis is an integral yet distinct part of the cellular program to overcome ER stress.

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    • "One mode of size control invokes component-mediated regulation, whereby levels of structural components, such as proteins and lipids, determine the organelle volume/size (Chan and Marshall, 2010; Goehring and Hyman, 2012). For single-copy organelles, component upregulation can thus lead to expansion, as in the case of the ER (Kirk et al., 2010; Schuck et al., 2009), whereas in the case of multicopy organelles, it can modulate the combined compartment volume by adjusting the number, as lysosomes do (Sardiello et al., 2009). "
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    • "). From the proliferation of the ER network at the onset of the UPR one can predict that abundance and/or size of lipid droplets would be reduced because storage lipids are consumed for the production of membrane lipids (Bernales et al., 2006; Schuck et al., 2009). Persisting UPR activity, however, also reduces the cellular growth rate and thus dampens the demand for lipid metabolites. "
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    • "A misbalance between SFAs and UFAs in the diet and, consequently, cells induces ER stress and can lead to cell death (Kim et al., 2008). Conversely, a massive induction of ER stress is counterbalanced by the increased utilization of FAs for lipid synthesis and expansion of the ER (Bernales et al., 2006; Schuck et al., 2009). This introduces a conundrum surrounding the nature by which ER stress is modulated by lipid species. "
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