PUBLICATION
Lysophospholipid acyltransferase-mediated formation of saturated glycerophospholipids maintained cell membrane integrity for hypoxic adaptation
- Authors
- Li, Q., Xia, Z., Wu, Y., Ma, Y., Zhang, D., Wang, S., Fan, J., Xu, P., Li, X., Bai, L., Zhou, X., Xue, M.
- ID
- ZDB-PUB-240412-1
- Date
- 2024
- Source
- The FEBS journal 291(14): 3191-3210 (Journal)
- Registered Authors
- Keywords
- DPPC, cell membrane integrity, hypoxic adaptation, lysophospholipid acyltransferase, multi‐omics
- MeSH Terms
-
- Humans
- Animals
- 1-Acylglycerophosphocholine O-Acyltransferase*/genetics
- 1-Acylglycerophosphocholine O-Acyltransferase*/metabolism
- 1,2-Dipalmitoylphosphatidylcholine/chemistry
- 1,2-Dipalmitoylphosphatidylcholine/metabolism
- Adaptation, Physiological/genetics
- Cell Membrane*/metabolism
- Intestinal Mucosa/metabolism
- Hypoxia/genetics
- Hypoxia/metabolism
- Glycerophospholipids*/metabolism
- Mice
- Saccharomyces cerevisiae/genetics
- Saccharomyces cerevisiae/growth & development
- Saccharomyces cerevisiae/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 38602252 Full text @ FEBS J.
Citation
Li, Q., Xia, Z., Wu, Y., Ma, Y., Zhang, D., Wang, S., Fan, J., Xu, P., Li, X., Bai, L., Zhou, X., Xue, M. (2024) Lysophospholipid acyltransferase-mediated formation of saturated glycerophospholipids maintained cell membrane integrity for hypoxic adaptation. The FEBS journal. 291(14):3191-3210.
Abstract
Adaptation to hypoxia has attracted much public interest because of its clinical significance. However, hypoxic adaptation in the body is complicated and difficult to fully explore. To explore previously unknown conserved mechanisms and key proteins involved in hypoxic adaptation in different species, we first used a yeast model for mechanistic screening. Further multi-omics analyses in multiple species including yeast, zebrafish and mice revealed that glycerophospholipid metabolism was significantly involved in hypoxic adaptation with up-regulation of lysophospholipid acyltransferase (ALE1) in yeast, a key protein for the formation of dipalmitoyl phosphatidylcholine [DPPC (16:0/16:0)], which is a saturated phosphatidylcholine. Importantly, a mammalian homolog of ALE1, lysophosphatidylcholine acyltransferase 1 (LPCAT1), enhanced DPPC levels at the cell membrane and exhibited the same protective effect in mammalian cells under hypoxic conditions. DPPC supplementation effectively attenuated growth restriction, maintained cell membrane integrity and increased the expression of epidermal growth factor receptor under hypoxic conditions, but unsaturated phosphatidylcholine did not. In agreement with these findings, DPPC treatment could also repair hypoxic injury of intestinal mucosa in mice. Taken together, ALE1/LPCAT1-mediated DPPC formation, a key pathway of glycerophospholipid metabolism, is crucial for cell viability under hypoxic conditions. Moreover, we found that ALE1 was also involved in glycolysis to maintain sufficient survival conditions for yeast. The present study offers a novel approach to understanding lipid metabolism under hypoxia and provides new insights into treating hypoxia-related diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping