Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Direkt zur Navigaton springen.
Direkt zum Inhalt springen.

Navigation/Suche

"Köpfe" der aktuellen Meldungen:

Nina Höller

Nariae Baik-Schneditz

Bernhard Schwaberger

Lukas Peter Mileder

Niels Hammer

Daniel Scherr

Gerhard Pichler

Roland Malli

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Zhu, XG; Nicholson Puthenveedu, S; Shen, Y; La, K; Ozlu, C; Wang, T; Klompstra, D; Gultekin, Y; Chi, J; Fidelin, J; Peng, T; Molina, H; Hang, HC; Min, W; Birsoy, K.
CHP1 Regulates Compartmentalized Glycerolipid Synthesis by Activating GPAT4.
MOL CELL. 2019; 74(1): 45-58. Doi: 10.1016/j.molcel.2019.01.037 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-Autor*innen der Med Uni Graz: Nicholson Puthen Veedu Shirony
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
Abstract:: Cells require a constant supply of fatty acids to survive and proliferate. Fatty acids incorporate into membrane and storage glycerolipids through a series of endoplasmic reticulum (ER) enzymes, but how these enzymes are regulated is not well understood. Here, using a combination of CRISPR-based genetic screens and unbiased lipidomics, we identified calcineurin B homologous protein 1 (CHP1) as a major regulator of ER glycerolipid synthesis. Loss of CHP1 severely reduces fatty acid incorporation and storage in mammalian cells and invertebrates. Mechanistically, CHP1 binds and activates GPAT4, which catalyzes the initial rate-limiting step in glycerolipid synthesis. GPAT4 activity requires CHP1 to be N-myristoylated, forming a key molecular interface between the two proteins. Interestingly, upon CHP1 loss, the peroxisomal enzyme, GNPAT, partially compensates for the loss of ER lipid synthesis, enabling cell proliferation. Thus, our work identifies a conserved regulator of glycerolipid metabolism and reveals plasticity in lipid synthesis of proliferating cells. Copyright © 2019 Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing): 3T3 Cells -; Acyltransferases - genetics; Acyltransferases - metabolism; Animals -; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cell Proliferation -; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Drosophila melanogaster -; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - enzymology; Endoplasmic Reticulum - pathology; Enzyme Activation -; Gene Expression Regulation, Enzymologic -; Glycerides - biosynthesis; Glycerol-3-Phosphate O-Acyltransferase - genetics; Glycerol-3-Phosphate O-Acyltransferase - metabolism; HEK293 Cells -; HeLa Cells -; Hep G2 Cells -; Humans -; Jurkat Cells -; Lipogenesis - drug effects; Lipogenesis - genetics; Mice -; Palmitic Acid - toxicity; Protein Binding -