Phospholipid homeostasis in phosphatidylserine synthase-2-deficient mice

Phosphatidylethanolamine Deficiency in Mammalian Mitochondria Impairs Oxidative Phosphorylation and Alters Mitochondrial Morphology

“…Moreover, elimination of PSD in mice, in which PE synthesis from CDP-ethanolamine was active, was embryonic lethal establishing an absolute requirement for PSD in mice (1). However, Pisd ϩ/Ϫ mice that expressed 50% of normal Pisd mRNA and PSD activity were viable, and the mtPE content of tissues was normal (1,57). We therefore tested the hypothesis that reduction of mtPE synthesis by Ͼ50% in CHO cells would decrease mtPE content and impair mitochondrial morphology and function.…”

“…Remarkably, however, E. coli cells survive when PE, normally the most abundant phospholipid, is reduced to 0.007% of total phospholipids (56). PSD is required for mouse development because disruption of the mouse Pisd gene was embryonic lethal and profoundly altered mitochondrial morphology, even when PE was actively made from CDPethanolamine (1,57). Moreover, global disruption of the CDPethanolamine pathway for PE synthesis in mice is also embryonic lethal (58) demonstrating that both major PE biosynthetic pathways are required for mouse viability.…”

Thematic Review Series: Glycerolipids. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids

“…Despite a marked reduction in total PS synthase activity in all PS synthase-2-deficient mouse tissues, the amounts of PS and PE were normal. Hepatocytes from Pss2 2/2 mice are apparently able to maintain PS levels by increasing the activity, but not the mRNA, of PS synthase-1 and by concomitantly attenuating the rate of PS degradation (103). Viable mice lacking PS synthase-1 have also now been generated and exhibit no obvious phenotype; male and female Pss1 2/2 mice are fertile (D. Arikketh and J. E. Vance, unpublished data).…”

The CDP-ethanolamine Pathway and Phosphatidylserine Decarboxylation Generate Different Phosphatidylethanolamine Molecular Species

“…1D; the unexpected appearance of d 2 -PtdSer will be explained under "Discussion" and is corrected for, see "Experimental Procedures"). In addition to PtdSer decarboxylation, (labeled) serine can be incorporated into PtdEtn via two other routes; (i) it can enter the CDP-Etn pathway as (labeled) phosphoethanolamine, generated as an intermediate of sphingomyelin metabolism (30), and (ii) it can be incorporated into the diacylglycerol moiety (31). However, experiments with ␤-chloro-L-alanine, a potent inhibitor of sphingomyelin synthesis (32), revealed that phosphoethanolamine liberated from sphingomyelin breakdown only marginally (Ͻ2%) contributed to serine labeling of PtdEtn in our experimental system (data not shown).…”