Universität zu Köln

Schuetter, Maximilian, Giavalisco, Patrick, Brodesser, Susanne and Graef, Martin (2020). Local Fatty Acid Channeling into Phospholipid Synthesis Drives Phagophore Expansion during Autophagy. Cell, 180 (1). S. 135 - 164. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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Abstract

Autophagy is a conserved catabolic homeostasis process central for cellular and organismal health. During autophagy, small single-membrane phagophores rapidly expand into large double-membrane autophagosomes to encapsulate diverse cargoes for degradation. It is thought that autophagic membranes are mainly derived from preformed organelle membranes. Instead, here we delineate a pathway that expands the phagophore membrane by localized phospholipid synthesis. Specifically, we find that the conserved acyl-CoA synthetase Faa1 accumulates on nucleated phagophores and locally activates fatty acids (FAs) required for phagophore elongation and autophagy. Strikingly, using isotopic FA tracing, we directly show that Faa1 channels activated FAs into the synthesis of phospholipids and promotes their assembly into autophagic membranes. Indeed, the first committed steps of de novo phospholipid synthesis at the ER, which forms stable contacts with nascent autophagosomes, are essential for autophagy. Together, our work illuminates how cells spatially tune synthesis and flux of phospholipids for autophagosome biogenesis during autophagy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schuetter, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Giavalisco, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Graef, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-349088
DOI:	10.1016/j.cell.2019.12.005
Journal or Publication Title:	Cell
Volume:	180
Number:	1
Page Range:	S. 135 - 164
Date:	2020
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1097-4172
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MEMBRANE CONTACT SITES; ACYL-COA SYNTHETASE; COENZYME-A-SYNTHETASE; ER-EXIT SITES; SACCHAROMYCES-CEREVISIAE; ENDOPLASMIC-RETICULUM; SEC PROTEINS; PHOSPHATIDYLINOSITOL 3-PHOSPHATE; SIGNATURE MOTIF; LIPID DROPLETS Multiple languages Biochemistry & Molecular Biology; Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34908