Plasmalogen homeostasis – regulation of plasmalogen biosynthesis and its physiological consequence in mammals

Abstract

Plasmalogens, mostly ethanolamine‐containing alkenyl ether phospholipids, are a major subclass of glycerophospholipids. Plasmalogen synthesis is initiated in peroxisomes and completed in the endoplasmic reticulum. The absence of plasmalogens in several organs of peroxisome biogenesis‐defective patients suggests that the de novo synthesis of plasmalogens plays a pivotal role in its homeostasis in tissues. Plasmalogen synthesis is regulated by modulating the stability of fatty acyl‐CoA reductase 1 on peroxisomal membranes, a rate‐limiting enzyme in plasmalogen synthesis, by sensing plasmalogens in the inner leaflet of plasma membranes. Dysregulation of plasmalogen homeostasis impairs cholesterol biosynthesis by altering the stability of squalene monooxygenase, a key enzyme in cholesterol biosynthesis, implying physiological consequences of plasmalogen homeostasis with respect to cholesterol metabolism in cells, as well as in organs such as the liver.

Lipidomics unveils lipid dyshomeostasis and low circulating plasmalogens as biomarkers in a monogenic mitochondrial disorder

“…Therefore, possible explanations include a mismatch between their hepatic export via lipoproteins and extrahepatic uptake and/or enhanced hepatic synthesis as a compensatory mechanism to normalize their blood levels. The biosynthesis of plasmalogens is regulated by their intracellular levels through a negative feedback mechanism involving the enzyme FAR1 (33,34,44,45). This plasmalogen-sensing mechanism occurs in the inner leaflet of the plasma membrane and the signal is subsequently transferred to peroxisomes (33).…”

The role of lipid species in membranes and cancer-related changes

“…Although ether lipids have been estimated to represent 18% of total phospholipids in humans [33], they have so far not obtained much attention, and they are still hardly mentioned in text books. Ether lipids have been reported to be involved in membrane trafficking, cell signaling, to possibly function as cellular antioxidants and to be enriched in cancer cells; we refer to the following review articles regarding ether lipids [33][34][35][36]. Importantly, the ether lipids are required for generation of the alkyl-containing glycosylphosphatidylinositol (GPI)-anchored proteins, which can be present in lipid rafts [26,37].…”

Plasma metabolomics analysis of endogenous and exogenous metabolites in the rat after administration of Lonicerae Japonicae Flos

“…Their content increased at D1 and D3, and had similar levels at D5. Plasmalogen synthesis is initiated in peroxisomes and completed in the endoplasmic reticulum, and they can act as endogenous plasma antioxidants and regulate the cholesterol metabolism (Braverman & Moser, ; Honsho & Fujiki, ). LJF activates the synthesis of plasmalogen and tends to plasmalogen homeostasis at D5.…”