Journal
FEBS LETTERS
Volume 591, Issue 18, Pages 2720-2729Publisher
WILEY
DOI: 10.1002/1873-3468.12743
Keywords
cholesterol metabolism; Far1; plasmalogen homeostasis
Funding
- Takeda Science Foundation [23570236, 26440102, 17K07337, 24247038, 25112518, 25116717, 26116007, 15K14511, 15K21743, 17H03675]
- Naito Foundation
- Japan Foundation for Applied Enzymology
- Novartis Foundation (Japan) for the Promotion of Science
- Grants-in-Aid for Scientific Research [17K07337, 17H03675, 26116007, 15K21743] Funding Source: KAKEN
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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.
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