Biosynthesis of ether-phospholipids including plasmalogens, peroxisomes and human disease: new insights into an old problem

摘要

Ether-phospholipids represent an important subclass of phospholipids in animal cell membranes characterized by the presence of an ether bond at the sn-l position and the enrichment of PUFAs at the sn-2 position. Of the different ether-phospholipids, plasmalogens are the most abundant form and their importance to human health is emphasized by the severe clinical presentation of patients with defects in the biosynthesis of plasmalogens or patients with defects in the biogenesis of peroxisomes, since the biosynthesis of plasmalogens requires functional peroxisomes. Inferred from the pathology observed in patients, plasmalogens play an important role in bone, eye and brain development. Owing to their structure and composition, plasmalogens have been found to function as antioxidants, as mediators of membrane structure and dynamics, and as mediators in signal transduction. Nevertheless, it is still unresolved and poorly understood how the different roles or functions attributed to plasmalogens mediate normal cell physiology and how the deficiency in plasmalogens leads to the abnormal development and severe pathology of target tissues. With the generation of mouse models with defects in the biosynthesis of plasmalogens, new insights and knowledge are expected.