Phosphatidylethanolamine Metabolism in Health and Disease

Abstract

Phosphatidylethanolamine (PE) is the second most abundant glycerophospholipid in eukaryotic cells. The existence of four only partially redundant biochemical pathways that produce PE, highlights the importance of this essential phospholipid. The CDP-ethanolamine and phosphatidylserine decarboxylase pathways occur in different subcellular compartments and are the main sources of PE in cells. Mammalian development fails upon ablation of either pathway. Once made, PE has diverse cellular functions that include serving as a precursor for phosphatidylcholine and a substrate for important posttranslational modifications, influencing membrane topology, and promoting cell and organelle membrane fusion, oxidative phosphorylation, mitochondrial biogenesis, and autophagy. The importance of PE metabolism in mammalian health has recently emerged following its association with Alzheimer's disease, Parkinson's disease, nonalcoholic liver disease, and the virulence of certain pathogenic organisms.

The role of nonbilayer phospholipids in mitochondrial structure and function

“…Similar to biosynthetic regulation of CL, the phospholipid precursor inositol has been shown to supress Psd1 expression [57]. Thus, perturbation in Psd1 maturation or expression leads to a decrease in mitochondrial PE levels [58].…”

Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochromebc1complex function

“…The predominant pathways for PE production include the Kennedy pathway, which synthesizes PE through the stepwise conjugation of CDP-ethanolamine to diacylglycerol (DAG) and the Psd pathway which utilizes phosphatidylserine (PS) as a substrate to generate PE (1). In multicellular organisms, preference for either the Kennedy pathway or the Psd pathway varies between tissues and cell types (6). Notably, deletion of either pathway is lethal during murine embryogenesis, highlighting the importance of PE generation in both the ER and mitochondrial compartments for development (7, 8).…”

“…Conservation of the Psd pathway from bacteria to humans likely reflects the endosymbiotic origin of mitochondria which in turn suggests that mitochondrial PS and PE metabolism has been preserved to optimize mitochondrial performance (6). Indeed, deletion of phosphatidylserine decarboxylase ( Pisd in mouse and humans and PSD1 in yeast) in eukaryotic cells decreases cellular growth, impairs oxidative phosphorylation, produces aberrant mitochondrial morphology, and diminishes PE levels in cells and mitochondria (7, 9–12).…”

Targeting Membrane Lipid a Potential Cancer Cure?

“…In addition, PE is also abundant in the inner membrane of mitochondria (Vance, 2008). Besides functioning as a membrane structural element, the evidence suggests that PE participates in many important pathophysiological cellular processes (Vance, 2008; Calzada et al, 2016). It has been demonstrated that translocation and redistribution of PE occurs during a number of distinct biological events: (1) cell division where it is externalized at the cleavage furrow (Emoto et al, 1996); (2) cell death (for which exposure of PE to extracellular environment is a molecular marker) (Emoto et al, 1997); (3) anticoagulant mechanism where PE acts as a cofactor for protein C (Tian et al, 2006).…”