Related Experiment Video
Updated: Feb 28, 2026

Metabolic Characterization of Polarized M1 and M2 Bone Marrow-derived Macrophages Using Real-time Extracellular Flux Analysis
Published on: November 28, 2015
ATF2-LPCAT1-mediated PKM2 acetylation links cholesterol stress to macrophage metabolic reprogramming and functional
Huiling Cao1, Shujun Ma2, Miaomiao Tian1
1Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Abstract:
Pyruvate kinase M2 (PKM2) regulates cellular metabolism under stress. However, mechanisms involving PKM2 modification in cholesterol-loaded macrophages remain unclear. In this study, we first characterized the impact of cholesterol loading on macrophage functional and metabolic alterations. Although cholesterol loading did not alter PKM2 expression, it regulated PKM2 function by promoting its acetylation. Specifically, PKM2 acetylation at lysine 433 (K433) exacerbated cholesterol-induced metabolic disorders and inflammation, whereas K433 mutations ameliorated these effects. Mechanistically, cholesterol activated the p38 mitogen-activated protein kinase (MAPK) pathway, inducing activating transcription factor 2 (ATF2) and upregulating lysophosphatidylcholine acyltransferase 1 (LPCAT1) to promote PKM2 acetylation. Collectively, PKM2 acetylation mediates cholesterol-induced metabolic and functional reprogramming in macrophages, highlighting the novel p38-ATF2-LPCAT1-PKM2 axis in immune stress signaling.
Related Concept Videos
Lipid Catabolism
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
The Unfolded Protein Response
Cholesterol: Significance and Regulation
Considering cholesterol and...
cAMP-dependent Protein Kinase Pathways
Overview of Fatty Acid Metabolism
Fatty acids are catabolized in a process called beta-oxidation, which takes place in the matrix of the mitochondria and converts their fatty acid chains into two-carbon units of acetyl groups. The acetyl...

