Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Nat Commun ; 11(1): 4480, 2020 09 08.
Article in English | MEDLINE | ID: mdl-32900992

ABSTRACT

Macroautophagy initiates by formation of isolation membranes, but the source of phospholipids for the membrane biogenesis remains elusive. Here, we show that autophagic membranes incorporate newly synthesized phosphatidylcholine, and that CTP:phosphocholine cytidylyltransferase ß3 (CCTß3), an isoform of the rate-limiting enzyme in the Kennedy pathway, plays an essential role. In starved mouse embryo fibroblasts, CCTß3 is initially recruited to autophagic membranes, but upon prolonged starvation, it concentrates on lipid droplets that are generated from autophagic degradation products. Omegasomes and isolation membranes emanate from around those lipid droplets. Autophagy in prolonged starvation is suppressed by knockdown of CCTß3 and is enhanced by its overexpression. This CCTß3-dependent mechanism is also present in U2OS, an osteosarcoma cell line, and autophagy and cell survival in starvation are decreased by CCTß3 depletion. The results demonstrate that phosphatidylcholine synthesis through CCTß3 activation on lipid droplets is crucial for sustaining autophagy and long-term cell survival.


Subject(s)
Autophagy/physiology , Choline-Phosphate Cytidylyltransferase/metabolism , Fibroblasts/cytology , Fibroblasts/metabolism , Animals , Autophagosomes/metabolism , Cell Line, Tumor , Cell Survival , Choline-Phosphate Cytidylyltransferase/antagonists & inhibitors , Choline-Phosphate Cytidylyltransferase/genetics , Culture Media , Enzyme Activation , Gene Knockdown Techniques , Humans , Lipid Droplets/metabolism , Mice , Models, Biological , Mouse Embryonic Stem Cells/cytology , Mouse Embryonic Stem Cells/metabolism , Osteosarcoma/metabolism , Osteosarcoma/pathology , Phosphatidylcholines/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...