Universität zu Köln

Wilson-Zbinden, Caroline, dos Santos, Aline Xavier da Silveira, Stoffel-Studer, Ingrid, van der Vaart, Aniek, Hofmann, Kay ORCID: 0000-0002-2289-9083, Reggiori, Fulvio ORCID: 0000-0003-2652-2686, Riezman, Howard ORCID: 0000-0003-4680-9422, Kraft, Claudine and Peter, Matthias ORCID: 0000-0002-2160-6824 (2015). Autophagy Competes for a Common Phosphatidylethanolamine Pool with Major Cellular PE-Consuming Pathways in Saccharomyces cerevisiae. Genetics, 199 (2). S. 475 - 486. BETHESDA: GENETICS SOCIETY AMERICA. ISSN 1943-2631

Full text not available from this repository.

Abstract

Autophagy is a highly regulated pathway that selectively degrades cellular constituents such as protein aggregates and excessive or damaged organelles. This transport route is characterized by engulfment of the targeted cargo by autophagosomes. The formation of these double-membrane vesicles requires the covalent conjugation of the ubiquitin-like protein Atg8 to phosphatidylethanolamine (PE). However, the origin of PE and the regulation of lipid flux required for autophagy remain poorly understood. Using a genetic screen, we found that the temperature-sensitive growth and intracellular membrane organization defects of mcd4-174 and mcd4-P301L mutants are suppressed by deletion of essential autophagy genes such as ATG1 or ATG7. MCD4 encodes an ethanolamine phosphate transferase that uses PE as a precursor for an essential step in the synthesis of the glycosylphosphatidylinositol (GPI) anchor used to link a subset of plasma membrane proteins to lipid bilayers. Similar to the deletion of CHO2, a gene encoding the enzyme converting PE to phosphatidylcholine (PC), deletion of ATG7 was able to restore lipidation and plasma membrane localization of the GPI-anchored protein Gas1 and normal organization of intracellular membranes. Conversely, overexpression of Cho2 was lethal in mcd4-174 cells grown at restrictive temperature. Quantitative lipid analysis revealed that PE levels are substantially reduced in the mcd4-174 mutant but can be restored by deletion of ATG7 or CHO2. Taken together, these data suggest that autophagy competes for a common PE pool with major cellular PE-consuming pathways such as the GPI anchor and PC synthesis, highlighting the possible interplay between these pathways and the existence of signals that may coordinate PE flux.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wilson-Zbinden, Caroline UNSPECIFIED UNSPECIFIED UNSPECIFIED dos Santos, Aline Xavier da Silveira UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoffel-Studer, Ingrid UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Vaart, Aniek UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Kay UNSPECIFIED orcid.org/0000-0002-2289-9083 UNSPECIFIED Reggiori, Fulvio UNSPECIFIED orcid.org/0000-0003-2652-2686 UNSPECIFIED Riezman, Howard UNSPECIFIED orcid.org/0000-0003-4680-9422 UNSPECIFIED Kraft, Claudine UNSPECIFIED UNSPECIFIED UNSPECIFIED Peter, Matthias UNSPECIFIED orcid.org/0000-0002-2160-6824 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-413361
DOI:	10.1534/genetics.114.169797
Journal or Publication Title:	Genetics
Volume:	199
Number:	2
Page Range:	S. 475 - 486
Date:	2015
Publisher:	GENETICS SOCIETY AMERICA
Place of Publication:	BETHESDA
ISSN:	1943-2631
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GLYCOSYLPHOSPHATIDYLINOSITOL ANCHOR SYNTHESIS; ENDOPLASMIC-RETICULUM; ALPHA-MANNOSIDASE; GPI ANCHOR; YEAST; PROTEIN; BIOSYNTHESIS; CYTOPLASM; MUTANTS; MCD4P Multiple languages Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/41336