Metabolic routing maintains the unique fatty acid composition of phosphoinositides

EMBO Reports - Tập 23 Số 7 - 2022
Yeun Ju Kim1, Nivedita Sengupta1, Mira Sohn1, Amrita Mandal1, Joshua G. Pemberton1, Uimook Choi2, Tamás Balla1
1Section on Molecular Signal Transduction Program for Developmental Neuroscience NICHD National Institutes of Health Bethesda MD USA
2Genetic Immunotherapy Section Laboratory of Clinical Immunology and Microbiology NIAID National Institutes of Health Bethesda MD USA

Tóm tắt

AbstractPhosphoinositide lipids (PPIn) are enriched in stearic‐ and arachidonic acids (38:4) but how this enrichment is established and maintained during phospholipase C (PLC) activation is unknown. Here we show that the metabolic fate of newly synthesized phosphatidic acid (PA), the lipid precursor of phosphatidylinositol (PI), is influenced by the fatty acyl‐CoA used with preferential routing of the arachidonoyl‐enriched species toward PI synthesis. Furthermore, during agonist stimulation the unsaturated forms of PI(4,5P)2 are replenished significantly faster than the more saturated ones, suggesting a favored recycling of the unsaturated forms of the PLC‐generated hydrolytic products. Cytidine diphosphate diacylglycerol synthase 2 (CDS2) but not CDS1 was found to contribute to increased PI resynthesis during PLC activation. Lastly, while the lipid transfer protein, Nir2 is found to contribute to rapid PPIn resynthesis during PLC activation, the faster re‐synthesis of the 38:4 species does not depend on Nir2. Therefore, the fatty acid side‐chain composition of the lipid precursors used for PI synthesis is an important determinant of their metabolic fates, which also contributes to the maintenance of the unique fatty acid profile of PPIn lipids.

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Tập 23 Số 7

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