Open Close
Reference
Citation
Zhu, X.G., Nicholson Puthenveedu, S., Shen, Y., La, K., Ozlu, C., Wang, T., Klompstra, D., Gultekin, Y., Chi, J., Fidelin, J., Peng, T., Molina, H., Hang, H.C., Min, W., Birsoy, K. (2019). CHP1 Regulates Compartmentalized Glycerolipid Synthesis by Activating GPAT4.  Mol. Cell 74(1): 45--58.e7.
FlyBase ID
FBrf0242916
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC6450717 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mol. Cell
    Title
    Molecular Cell
    Publication Year
    1997-
    ISBN/ISSN
    1097-2765 1097-4164
    Data From Reference
    Genes (1)