ArticleCommunications biology2024
The gluconeogenesis enzyme PCK2 has a non-enzymatic role in proteostasis in endothelial cells.
Article in Communications biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Endothelial SLC25A13 links glutamine metabolism to angiogenesis.EMBO molecular medicine · 2026Article
- Single-Cell Metabolic Imaging Reveals Glycogen-Driven Adaptations in Endothelial Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The CSF Levels of Mitochondrial Phosphoenolpyruvate Carboxykinase 2 as a Novel Biomarker in Alzheimer's Disease.Molecular neurobiology · 2025Article
- Article
- Induction of plasmalemmal vesicle-associated protein exacerbates glomerular endothelial injury in thrombotic microangiopathy.American journal of physiology. Renal physiology · 2025Article
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
Endothelial cells (ECs) are highly glycolytic, but whether they generate glycolytic intermediates via gluconeogenesis (GNG) in glucose-deprived conditions remains unknown. Here, we report that glucose-deprived ECs upregulate the GNG enzyme PCK2 and rely on a PCK2-dependent truncated GNG, whereby lactate and glutamine are used for the synthesis of lower glycolytic intermediates that enter the serine and glycerophospholipid biosynthesis pathways, which can play key roles in redox homeostasis and phospholipid synthesis, respectively. Unexpectedly, however, even in normal glucose conditions, and independent of its enzymatic activity, PCK2 silencing perturbs proteostasis, beyond its traditional GNG role. Indeed, PCK2-silenced ECs have an impaired unfolded protein response, leading to accumulation of misfolded proteins, which due to defective proteasomes and impaired autophagy, results in the accumulation of protein aggregates in lysosomes and EC demise. Ultimately, loss of PCK2 in ECs impaired vessel sprouting. This study identifies a role for PCK2 in proteostasis beyond GNG.
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