Peds1-KO Mouse

Peds1, also known as plasmanylethanolamine desaturase 1 or TMEM189, is the enzyme responsible for introducing a vinyl ether double bond into plasmanylethanolamine phospholipids, thereby synthesizing plasmalogens, a subclass of ether lipids [2,3,4,5]. Plasmalogens have proposed roles in membrane organization, fluidity, signaling, and antioxidative functions, and abnormal levels are associated with various human pathologies [2,7].

Peds1 -deficient zebrafish larvae display delayed development, increased basal inflammation, normal hematopoietic stem and progenitor cell emergence, and cell-autonomous myeloid cell apoptosis. In inflammation models, they show impaired inflammation resolution, tissue regeneration, and abnormal immune cell recruitment [1]. Peds1-knockout mice have a growth phenotype and exhibit striking changes in lipid metabolism, with a strong reduction of plasmenyl lipids and a concomitant massive accumulation of plasmanyl lipids [3]. A single mutation of aspartate 100 in murine Peds1 leads to a total loss of its enzymatic activity [4]. Additionally, the rs6020298 GG genotype and G allele of Peds1 are significantly associated with an increased risk of developing Long COVID [6].

In conclusion, Peds1 is essential for plasmalogen biosynthesis and plays a crucial role in myeloid cell biology, inflammation, and lipid metabolism. Studies using gene-knockout models, such as zebrafish and mice, have revealed its functions in these biological processes and its potential association with diseases like Long COVID. Understanding Peds1 contributes to a better understanding of the underlying mechanisms of related diseases and may offer new insights for treatment strategies.

References:

1. Arroyo, Ana B, Tyrkalska, Sylwia D, Bastida-Martínez, Eva, Elías-Arnanz, Montserrat, Mulero, Victoriano. 2024. Peds1 deficiency in zebrafish results in myeloid cell apoptosis and exacerbated inflammation. In Cell death discovery, 10, 388. doi:10.1038/s41420-024-02141-w. https://pubmed.ncbi.nlm.nih.gov/39209813/

2. Padmanabhan, S, Monera-Girona, Antonio J, Pajares-Martínez, Elena, Fontes, Marta, Elías-Arnanz, Montserrat. 2022. Plasmalogens and Photooxidative Stress Signaling in Myxobacteria, and How it Unmasked CarF/TMEM189 as the Δ1'-Desaturase PEDS1 for Human Plasmalogen Biosynthesis. In Frontiers in cell and developmental biology, 10, 884689. doi:10.3389/fcell.2022.884689. https://pubmed.ncbi.nlm.nih.gov/35646900/

3. Lackner, Katharina, Sailer, Sabrina, van Klinken, Jan-Bert, Werner, Ernst R, Watschinger, Katrin. 2023. Alterations in ether lipid metabolism and the consequences for the mouse lipidome. In Biochimica et biophysica acta. Molecular and cell biology of lipids, 1868, 159285. doi:10.1016/j.bbalip.2023.159285. https://pubmed.ncbi.nlm.nih.gov/36690320/

4. Werner, Ernst R, Fernández-Quintero, Monica L, Hulo, Nicolas, Liedl, Klaus R, Watschinger, Katrin. 2022. Essential role of a conserved aspartate for the enzymatic activity of plasmanylethanolamine desaturase. In Cellular and molecular life sciences : CMLS, 79, 214. doi:10.1007/s00018-022-04238-w. https://pubmed.ncbi.nlm.nih.gov/35347434/

5. Yu, Jiahong, Qu, Liujing, Xia, Yan, Lu, Wenping, Chen, Yingyu. 2022. TMEM189 negatively regulates the stability of ULK1 protein and cell autophagy. In Cell death & disease, 13, 316. doi:10.1038/s41419-022-04722-y. https://pubmed.ncbi.nlm.nih.gov/35393404/

6. Udomsinprasert, Wanvisa, Nontawong, Nuttakant, Saengsiwaritt, Wacharapol, Chaikledkaew, Usa, Chantratita, Wasun. . Host genetic polymorphisms involved in long-term symptoms of COVID-19. In Emerging microbes & infections, 12, 2239952. doi:10.1080/22221751.2023.2239952. https://pubmed.ncbi.nlm.nih.gov/37497655/

7. Koch, Jakob, Watschinger, Katrin, Werner, Ernst R, Keller, Markus A. 2022. Tricky Isomers-The Evolution of Analytical Strategies to Characterize Plasmalogens and Plasmanyl Ether Lipids. In Frontiers in cell and developmental biology, 10, 864716. doi:10.3389/fcell.2022.864716. https://pubmed.ncbi.nlm.nih.gov/35573699/