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Membrane Dynamics of Lipid Droplet-Mediated ER Proteostasis in the Budding Yeast, Saccharomyces cerevisiae

57 Pages Posted: 11 Jun 2019 Sneak Peek Status: Review Complete

See all articles by Enrique Garcia

Enrique Garcia

Columbia University

Gary Tan

Columbia University - Department of Pathology and Cell Biology

Jason Vevea

Johns Hopkins University

J. Michael McCaffery

Johns Hopkins University

Istvan R. Boldogh

Columbia University - Department of Pathology and Cell Biology

Liza A. Pon

Columbia University - Department of Pathology and Cell Biology

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Abstract

Our previous studies revealed a novel mechanism for lipid droplet (LD)-mediated ER proteostasis that is stimulated by lipid imbalance-induced ER stress. They support the model that this stressor stimulates removal of proteins from the ER by LDs and degradation of LDs by microlipophagy, autophagosome-independent LD uptake into the vacuole (the yeast lysosome). Here, we show that a similar mechanism occurs during dithiothreitol (DTT)- or tunicamycin (TM)-induced ER stress. We identified proteins that are possible targets for LD-mediated ER proteostasis and find that the targets vary in response to different ER stressors. Our live-cell imaging studies provide the first direct evidence that one of these targets (Nup159p) can be removed from ER membranes by LDs, moves with LDs through the cytosol and co-localizes with LDs in the vacuolar lumen. Thus, we obtained the first direct evidence that LDs can mediate ER proteostasis. Microlipophagy induced by all stressors studied does not require core ATG genes and can occur in the absence of liquid-ordered microdomains (Lo) in the vacuolar membrane. Instead, we find that the endosome sorting complexes required for transport (ESCRT) I-III are up-regulated, recruited to vacuolar membranes, and required for microlipophagy in response to all ER stressors analyzed. Interestingly, ESCRT 0 is not required for DTT-induced microlipophagy but is required for microlipophagy induced by other stressors studied. Our imaging studies also revealed an unexpected role for vacuolar fusion in remodeling and invagination of the vacuolar membrane during microlipophagy.

Keywords: microautophagy, ESCRT, vacuole, ER stress, unfolded protein response, ERAD, lipid droplet proteome

Suggested Citation

Garcia, Enrique and Tan, Gary and Vevea, Jason and McCaffery, J. Michael and Boldogh, Istvan R. and Pon, Liza A., Membrane Dynamics of Lipid Droplet-Mediated ER Proteostasis in the Budding Yeast, Saccharomyces cerevisiae (June 10, 2019). Available at SSRN: https://ssrn.com/abstract=3401844 or http://dx.doi.org/10.2139/ssrn.3401844
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Enrique Garcia

Columbia University

Gary Tan

Columbia University - Department of Pathology and Cell Biology

New York, NY 10032
United States

Jason Vevea

Johns Hopkins University ( email )

Baltimore, MD 20036-1984
United States

J. Michael McCaffery

Johns Hopkins University

Baltimore, MD 20036-1984
United States

Istvan R. Boldogh

Columbia University - Department of Pathology and Cell Biology

New York, NY 10032
United States

Liza A. Pon (Contact Author)

Columbia University - Department of Pathology and Cell Biology ( email )

New York, NY 10032
United States

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