Universität zu Köln

Velazquez, Ariadna R., Tatsuta, Takashi, Ghillebert, Ruben, Drescher, Ingmar and Graef, Martin (2016). Lipid droplet-mediated ER homeostasis regulates autophagy and cell survival during starvation. J. Cell Biol., 212 (6). S. 621 - 632. NEW YORK: ROCKEFELLER UNIV PRESS. ISSN 1540-8140

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Abstract

Lipid droplets (LDs) are conserved organelles for intracellular neutral lipid storage. Recent studies suggest that LDs function as direct lipid sources for autophagy, a central catabolic process in homeostasis and stress response. Here, we demonstrate that LDs are dispensable as a membrane source for autophagy, but fulfill critical functions for endoplasmic reticulum (ER) homeostasis linked to autophagy regulation. In the absence of LDs, yeast cells display alterations in their phospholipid composition and fail to buffer de novo fatty acid (FA) synthesis causing chronic stress and morphologic changes in the ER. These defects compromise regulation of autophagy, including formation of multiple aberrant Atg8 puncta and drastically impaired autophagosome biogenesis, leading to severe defects in nutrient stress survival. Importantly, metabolically corrected phospholipid composition and improved FA resistance of LD-deficient cells cure autophagy and cell survival. Together, our findings provide novel insight into the complex interrelation between LD-mediated lipid homeostasis and the regulation of autophagy potentially relevant for neurodegenerative and metabolic diseases.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Velazquez, Ariadna R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tatsuta, Takashi UNSPECIFIED UNSPECIFIED UNSPECIFIED Ghillebert, Ruben UNSPECIFIED UNSPECIFIED UNSPECIFIED Drescher, Ingmar UNSPECIFIED UNSPECIFIED UNSPECIFIED Graef, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-281476
DOI:	10.1083/jcb.201508102
Journal or Publication Title:	J. Cell Biol.
Volume:	212
Number:	6
Page Range:	S. 621 - 632
Date:	2016
Publisher:	ROCKEFELLER UNIV PRESS
Place of Publication:	NEW YORK
ISSN:	1540-8140
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language YEAST SACCHAROMYCES-CEREVISIAE; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; PHOSPHATIDIC-ACID; NEURODEGENERATIVE DISEASE; BIOGENESIS; METABOLISM; MACROAUTOPHAGY; PATHWAY; OBESITY Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28147