
@article {159722,
	title = {Phosphoinositide acyl chain diversity: comparative analysis across species and mouse tissues.},
	journal = {Biochim Biophys Acta Mol Cell Biol Lipids},
	volume = {1870},
	year = {2025},
	month = {2025 Aug},
	pages = {159640},
	abstract = {<p>Cells create acyl chain compositions for their phosphoinositide (PIPn) pools that are distinct from other phospholipid classes. While some lower eukaryotes present highly heterogeneous PIPn (e.g., yeast, fly), more complex organisms typically display PIPn enriched in fewer molecular species (e.g., the C38:4 species in fish, frog and mice). A comprehensive analysis of murine tissues (using both LC-MS/MS and MSI) confirms a general enrichment for C38:4-PIPn but also highlights the existence of several cell populations with strikingly divergent acyl chain compositions, characterised by the prevalence of shorter-chain, more saturated species (e.g., C32:0 in the testes and C34:1 in the prostate). The evolutionary pressures driving the creation of these specific acyl chain compositions are still unclear; current evidence suggests there is probably a balance to be achieved in different cell types between the biophysical constraints imposed by PIPn as membrane-captive {\textquoteright}messengers{\textquoteright} (e.g., flexibility in head group presentation in different membrane environments), the demand for substantial de novo lipid synthesis (e.g., in rapid membrane expansion), the need for acyl chain remodelling (e.g., in molecular segregation of functional pools) and fatty acid availability. Moreover, it would appear inevitable that this balance will be distorted under most cell culture conditions in vitro.</p>
},
	keywords = {Animals, Male, Mice, Phosphatidylinositols, Species Specificity, Tandem Mass Spectrometry},
	issn = {1879-2618},
	doi = {10.1016/j.bbalip.2025.159640},
	author = {Barneda, David and Janardan, Vishnu and Swales, John and Ciaccia, Maria and Goodwin, Richard and Cosulich, Sabina and Raghu, Padinjat and Clark, Jonathan and Stephens, Len and Hawkins, Phillip}
}
@article {149383,
	title = {CDS2 expression regulates de novo phosphatidic acid synthesis.},
	journal = {Biochem J},
	volume = {481},
	year = {2024},
	month = {2024 Oct 16},
	pages = {1449-1473},
	abstract = {<p>CDS enzymes (CDS1 and 2 in mammals) convert phosphatidic acid (PA) to CDP-DG, an essential intermediate in the de novo synthesis of PI. Genetic deletion of CDS2 in primary mouse macrophages resulted in only modest changes in the steady-state levels of major phospholipid species, including PI, but substantial increases in several species of PA, CDP-DG, DG and TG. Stable isotope labelling experiments employing both 13C6- and 13C6D7-glucose revealed loss of CDS2 resulted in a minimal reduction in the rate of de novo PI synthesis but a substantial increase in the rate of de novo PA synthesis from G3P, derived from DHAP via glycolysis. This increased synthesis of PA provides a potential explanation for normal basal PI synthesis in the face of reduced CDS capacity (via increased provision of substrate to CDS1) and increased synthesis of DG and TG (via increased provision of substrate to LIPINs). However, under conditions of sustained GPCR-stimulation of PLC, CDS2-deficient macrophages were unable to maintain enhanced rates of PI synthesis via the {\textquoteright}PI cycle{\textquoteright}, leading to a substantial loss of PI. CDS2-deficient macrophages also exhibited significant defects in calcium homeostasis which were unrelated to the activation of PLC and thus probably an indirect effect of increased basal PA. These experiments reveal that an important homeostatic response in mammalian cells to a reduction in CDS capacity is increased de novo synthesis of PA, likely related to maintaining normal levels of PI, and provides a new interpretation of previous work describing pleiotropic effects of CDS2 deletion on lipid metabolism/signalling.</p>
},
	keywords = {Animals, Calcium, Diacylglycerol Cholinephosphotransferase, Macrophages, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphatidic Acids},
	issn = {1470-8728},
	doi = {10.1042/BCJ20240456},
	author = {Collins, Daniel M and Janardan, Vishnu and Barneda, David and Anderson, Karen E and Niewczas, Izabella and Taylor, Diane and Qiu, Danye and Jessen, Henning J and Lopez-Clavijo, Andrea F and Walker, Simon and Raghu, Padinjat and Clark, Jonathan and Stephens, Len R and Hawkins, Phillip T}
}
