Biochimica et biophysica acta. Molecular and cell biology of lipids最新文献

{"title":"Nuclear phosphoinositides: An exploration into their regulation, roles and physico-chemical environment","authors":"Charlotte L. Collier ,&nbsp;Palita Udomjarumanee ,&nbsp;Lee Morgan ,&nbsp;Joaquin Cardenas Rodriguez ,&nbsp;Muhammad Bilal Qasim ,&nbsp;Bhavwanti Sheth ,&nbsp;Imogen Taylor ,&nbsp;Sonakshi Gehlot ,&nbsp;Stefano Leto ,&nbsp;Roberta Fiume ,&nbsp;Nullin Divecha","doi":"10.1016/j.bbalip.2026.159725","DOIUrl":"10.1016/j.bbalip.2026.159725","url":null,"abstract":"<div><div>Polyphosphoinositides are phospholipids consisting of a diacylglycerol backbone linked to an inositol headgroup that can be phosphorylated at three positions, generating seven distinct lipid species. Their levels are tightly regulated by coordinated kinase, phosphatase, and phospholipase activities, each responsive to diverse cellular cues. The functional diversity of phosphoinositides arises from their ability to bind specific protein domains, thereby influencing protein localisation, activity, and interaction networks. Although traditionally associated with membrane-bound compartments, phosphoinositides are also present within the nucleus, not only at the nuclear envelope but also within a variety of membrane-less nuclear structures. The identification of nuclear phosphoinositide-binding proteins has revealed that phosphoinositides contribute to the regulation of multiple nuclear processes, including transcription, RNA maturation and export, DNA damage responses, and broader nuclear stress signalling. In this review, we summarise the mechanisms by which nuclear phosphoinositides are generated, spatially organised, and interpreted by downstream effectors, and we highlight key outstanding questions that remain to be resolved.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 3","pages":"Article 159725"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipidomic analysis of phospholipids and transcript expression of lipid metabolism genes in the liver and muscle of Atlantic salmon fed microbial oil and canola oil","authors":"Mohamed Emam ,&nbsp;JuDong Yeo ,&nbsp;Stefanie M. Colombo ,&nbsp;Nigel Guerra ,&nbsp;Khalil Eslamloo ,&nbsp;Albert Caballero-Solares ,&nbsp;Matthew L. Rise ,&nbsp;Christopher C. Parrish","doi":"10.1016/j.bbalip.2026.159723","DOIUrl":"10.1016/j.bbalip.2026.159723","url":null,"abstract":"<div><div>The increasing global demand for aquaculture products requires sustainable fish feed strategies. This study investigated how replacing fish oil with microbial oil (MO) and canola oil (CO) combinations affects lipid metabolism and gene expression in Atlantic salmon (<em>Salmo salar</em>), correlating these changes with phospholipid profiles. Four isonitrogenous, isoenergetic diets were tested: 20% fish oil (FO); 10% fish oil +10% CO (FO/CO); 15% CO + 5% MO (CO/MO); and 10% CO + 10% MO (MO-10). After 16 weeks, liver and skeletal muscle tissues were sampled for lipidomics and gene expression analysis. Multivariate analysis revealed distinct dietary group separations. The CO/MO diet induced the highest hepatic expression of <em>de novo</em> lipogenesis gene <em>fatty acid synthase b</em> while suppressing fatty acid oxidation marker <em>acyl-CoA oxidase 1</em>, indicating lipid storage promotion. Inflammatory marker <em>arachidonate 12-lipoxygenase</em> was associated with groups with reduced ω3 LC-PUFA (FO/CO, CO/MO). Muscle tissue showed subtler but diet-specific gene expression patterns, with <em>de novo</em> lipogenesis genes (<em>stearoyl-CoA desaturase b</em>, <em>ATP citrate lyase 2</em>) associated with decreased ω3 LC-PUFA (i.e., EPA and DHA) and correlating with monounsaturated fatty acids. The MO-10 group mirrored FO-fed fish, demonstrating successful fish oil replacement at 10% inclusion. Lipidomic pathway analysis revealed diet-induced phospholipid remodelling, for example, enhanced PE-to-PC conversion in the FO/CO and CO/MO groups, suggesting membrane-fluidity and inflammatory modulation. These results demonstrate tissue-specific metabolic adaptations to alternative lipid sources, with 10% CO + 10% MO effectively substituting for fish oil while maintaining metabolic profiles in the trial timeline. The findings advance our understanding of lipid metabolism regulation in salmon and support sustainable feed development for aquaculture and enhanced nutritional quality of aquaculture products.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 3","pages":"Article 159723"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting peroxisomal fatty acid β-oxidation lowers fasting glucose by suppressing gluconeogenesis","authors":"Wei Zhang ,&nbsp;Yicong Li ,&nbsp;Yida Zhang,&nbsp;Haoya Yao,&nbsp;Yaoqing Wang,&nbsp;Ping Li,&nbsp;Xiao Zhang,&nbsp;Jia Zeng","doi":"10.1016/j.bbalip.2026.159727","DOIUrl":"10.1016/j.bbalip.2026.159727","url":null,"abstract":"<div><div>Fatty acids play an important role in regulating gluconeogenesis through the metabolite acetyl-CoA, however, the underlying mechanisms on how fatty acid oxidation provides acetyl-CoA for the stimulation of pyruvate carboxylase and gluconeogenesis are not fully demonstrated. As a fatty acid β-oxidation system exists in peroxisomes and the acetyl-CoA derived from peroxisomal β-oxidation can be transported into mitochondria through the intermediate acetyl-carnitine, we hypothesize that this β-oxidation system might play a role in regulating pyruvate carboxylase and gluconeogenesis. The study demonstrates a mechanism by which fatty acids activate pyruvate carboxylase through the acetyl-CoA derived from peroxisomal β-oxidation. Induction of peroxisomal fatty acid β-oxidation results in excessive generation of acetyl-carnitine, which significantly elevates liver acetyl-CoA level and stimulates pyruvate carboxylase and gluconeogenesis in fasting mice. Specific inhibition of peroxisomal β-oxidation suppresses glucose production and lowers fasting glucose by reducing acetyl-CoA generation in the liver of diabetic mice. It is proposed that induction of peroxisomal β-oxidation serves as a pathogenic mechanism for fatty acids induced hyperactivation of pyruvate carboxylase and gluconeogenesis and targeting peroxisomal β-oxidation might be a potential pathway in treating diabetes through reducing acetyl-CoA generation and suppressing gluconeogenesis.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 3","pages":"Article 159727"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat therapy attenuates hepatic lipid accumulation via CSAD-driven metabolic reprogramming of fatty acid oxidation","authors":"Ang Li ,&nbsp;Yaru Dai ,&nbsp;Yijun Luo ,&nbsp;Ge Liang ,&nbsp;Luolan Gui ,&nbsp;Xinyi Hu ,&nbsp;Xin Li ,&nbsp;Dingkun Zhang ,&nbsp;Wen Zheng ,&nbsp;Lu Zhang ,&nbsp;Yuanping Gao ,&nbsp;Meng Gong","doi":"10.1016/j.bbalip.2026.159722","DOIUrl":"10.1016/j.bbalip.2026.159722","url":null,"abstract":"<div><h3>Objective</h3><div>Non-alcoholic fatty liver disease (NAFLD) represents a significant global health challenge, predominantly managed through non-pharmacological interventions. Heat therapy (HT) has been shown to effectively reduce hepatic lipid accumulation; however, the underlying mechanisms remain incompletely understood. This study aims to elucidate the mechanism by liver metabolomics.</div></div><div><h3>Methods</h3><div>This animal study utilized a high-fat diet to induce hepatic lipid accumulation in mice, combined with long-term HT intervention. Subsequently, metabolomic profiling and Western blot analysis were performed to assess hepatic metabolic alterations and elucidate the underlying mechanisms of HT action, followed by in vitro validation using L02 human hepatocytes.</div></div><div><h3>Results</h3><div>HT significantly decreased body weight, fat levels, and hepatic lipid accumulation while preventing excessive glycogen depletion in HFD-fed mice. Metabolomics analysis revealed that HT reduced diacylglycerol (DAG), triacylglycerol (TAG), free fatty acids (FFA), and saturated ceramides (CER); it also increased taurine levels, enhanced the utilization of vitamins B2, B5, and B6, and corrected amino acid imbalances. Furthermore, HT upregulated the expression of CSAD, ACADL, and ATP5A. In vitro studies demonstrated that heat treatment increased CSAD levels in L02 cells. Overexpression of CSAD elevated taurine levels and, under palmitic acid induction, reduced FFA levels while upregulating VDAC1 and ATP5A.</div></div><div><h3>Conclusions</h3><div>HT enhances mitochondrial function and promotes fatty acid oxidation by upregulating taurine synthesis via CSAD, thereby inhibiting hepatic lipid accumulation and correcting metabolic disorders, ultimately improving NAFLD.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 3","pages":"Article 159722"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palmitoylation of C4BPA in porcine epididymosomes mitigates complement C4-mediated damage to sperm","authors":"Heran Cao ,&nbsp;Long Li ,&nbsp;Shujuan Liu ,&nbsp;Hongmei Mo ,&nbsp;Yan Li ,&nbsp;Huihui Gao ,&nbsp;Tianhao Yang ,&nbsp;Mengqi Huang ,&nbsp;Ye Gong ,&nbsp;Zifang Wu ,&nbsp;Tianqi Jin ,&nbsp;Yang Wang ,&nbsp;Weibing Qin ,&nbsp;Wuzi Dong","doi":"10.1016/j.bbalip.2026.159729","DOIUrl":"10.1016/j.bbalip.2026.159729","url":null,"abstract":"<div><div>Previous studies have revealed the expression of anti-complement factors on the surface of sperm across various species to resist attacks from complement components in reproductive tracts. Here we show that the anti-complement factor The caput of the porcine epididymis specifically expresses C4BPA, which is then transported to the surface of sperm via epididymosomes. The presence of C4BPA in epididymosomes depends on its palmitoylation modification, specifically at the Cys13 and Cys23 residues. ZDHHC8 has been pinpointed as the palmitoyl transferase that carries out this modification. Palmitoylated C4BPA in epididymosomes significantly resists attacks by complement C4 on sperm, maintaining porcine sperm motility. Our findings reveal a critical role for palmitoylated C4BPA in mitigating C4-mediated damage to sperm, highlighting its physiological relevance in preserving sperm motility and viability.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 3","pages":"Article 159729"},"PeriodicalIF":3.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of macroautophagy and microautophagic lipophagy by phosphatidylserine synthase Cho1 and external ethanolamine","authors":"Nanaru Mineoka ,&nbsp;Rikako Konishi ,&nbsp;Yuri Nakashima ,&nbsp;Moe Muramoto ,&nbsp;Kayoko Fukuda ,&nbsp;Sayuri Kuriyama ,&nbsp;Tatsunori Masatani ,&nbsp;Akikazu Fujita","doi":"10.1016/j.bbalip.2025.159702","DOIUrl":"10.1016/j.bbalip.2025.159702","url":null,"abstract":"<div><div>Phospholipids play crucial roles in autophagy; however, the underlying mechanisms remain elusive. We previously found that the phosphatidylserine (PtdSer) transporter Osh5 is critical for autophagosome formation. Therefore, in this study, we aimed to investigate the impact of the knockout of <em>cho1</em>, which encodes PtdSer synthase, on autophagy. Green fluorescent protein-autophagy-related gene 8 (GFP-Atg8) processing assay revealed a significant defect in the macroautophagic activity of the <em>cho1</em>∆ mutant, regardless of the presence or absence of ethanolamine (Etn). Notably, autophagosomes were absent in the cytosol, and macroautophagic bodies were not observed in the vacuoles of the starved <em>cho1</em>∆ mutant, underscoring the essential role of PtdSer synthesized using Cho1 in autophagosome biogenesis. In contrast, numerous microautophagic vesicles containing lipid droplets were observed in the vacuoles of <em>cho1</em>∆ mutants starved in the presence of Etn, suggesting the crucial role of phosphatidylethanolamine (PtdEtn) synthesized via the Kennedy pathway in microautophagic lipophagy when PtdSer synthesis using Cho1 is disrupted. Given recent evidence pointing to the involvement of the ubiquitination system in various autophagy-related processes, we also examined the role of ubiquitin-conjugating enzyme E2 gene <em>ubc4</em>. In addition, deletion of <em>ubc4</em> gene led to a pronounced reduction in microautophagic lipophagy in starved <em>cho1</em>∆ cells, but not in wild-type cells. Together, these observations highlight an essential role for Ubc4-mediated ubiquitination in driving vacuolar microautophagic lipophagy specifically under Cho1-deficient conditions.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 2","pages":"Article 159702"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphoinositides at 50: From minor lipids to master organizers of polarity","authors":"Ama Gassama-Diagne","doi":"10.1016/j.bbalip.2025.159707","DOIUrl":"10.1016/j.bbalip.2025.159707","url":null,"abstract":"<div><div>Phosphoinositides (PIs) have been at the center of cell signaling and membrane biology since Michell's proposal of the PI-cycle in 1975. Over the past fifty years, these quantitatively minor lipids have emerged as versatile molecular organizers, defining membrane identity, generating spatial cues, coordinating cytoskeletal dynamics and thus playing pivotal role in polarity. Studies in yeast, amoebae, and neutrophils demonstrated how localized PI pools regulate polarity and chemotaxis, providing a conceptual advance to tissue-level organization. In epithelia, PIs now stand as central determinants of apico-basal polarity and lumen morphogenesis through their cooperation with Rho GTPases, polarity complexes, and septins. This review highlights how these lipids shape our understanding of membrane dynamics and epithelial tissue organization. To conclude, this review underscores how alterations in the activities of these polarity regulators lead to abnormal epithelial morphogenesis and severe diseases such as cancer.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 2","pages":"Article 159707"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ACADVL upregulation is associated with placental ferroptosis in intrahepatic cholestasis of pregnancy","authors":"Mi Tang ,&nbsp;Jianghui Cai ,&nbsp;Ling Zhang ,&nbsp;Liling xiong ,&nbsp;Xuejia Gong ,&nbsp;Jinzhu Fu ,&nbsp;Peilin Wang ,&nbsp;Mengqiu Luo ,&nbsp;Hong Liu ,&nbsp;Ying Ye ,&nbsp;Min Yu ,&nbsp;Heng Yu ,&nbsp;ShaSha Xing ,&nbsp;Xiao Yang","doi":"10.1016/j.bbalip.2025.159711","DOIUrl":"10.1016/j.bbalip.2025.159711","url":null,"abstract":"<div><h3>Introduction</h3><div>Intrahepatic cholestasis of pregnancy (ICP) is a disorder characterized by maternal pruritus and elevated total bile acid concentrations during pregnancy, posing severe fetal risks associated with placental dysfunction. However, the mechanisms underlying ICP remain to be fully elucidated.</div></div><div><h3>Methods</h3><div>An integrated approach was employed, utilizing placental scRNA-seq, LC-MS/MS-based lipidomics, and public RNA-seq data. The AUCell package, PPI network analysis, Random Forest, Support Vector Machine, and LASSO regression analyses were utilized to explore mitochondrial functions and identify hub mitochondria-related genes (MRGs). KEGG, GSEA, and GSVA were employed to investigate potential biological mechanisms. Key findings were validated by immunohistochemistry, immunofluorescence, and western blotting. Reactive oxygen species (ROS), malondialdehyde (MDA) and transmission electron microscopy were utilized to evaluate oxidative stress levels, lipid peroxidation and conduct ultrastructural examinations of mitochondria, respectively.</div></div><div><h3>Results</h3><div>MRGs are primarily distributed in villous cytotrophoblast (VCT). KEGG analysis of VCT indicated a close association with oxidative phosphorylation, ROS, Lipid. ACADVL was identified as a hub MRG and was found increased in ICP placenta, particularly in VCT. Functional analysis of ACADVL^high VCT revealed enrichment in fatty acid metabolism and oxidative phosphorylation. Lipidomics identified substantial alterations in glycerophospholipid and glycerolipid metabolism, and polyunsaturated fatty acid (PUFA) metabolism pathways. Experimentally, we observed the mitochondrial ACADVL localization, increased DRP1, decreased MFN2 and GPX4, and increased ROS and MDA levels in ICP. Electron microscopy revealed ultrastructural features consistent with ferroptosis.</div></div><div><h3>Conclusion</h3><div>This study proposes a novel model linking ACADVL, lipid metabolism, mitochondrial dysfunction, and ferroptosis in ICP pathogenesis.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 2","pages":"Article 159711"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Valproate causes inositol depletion in yeast by decreasing levels of phosphatidic acid and increasing Opi1-mediated repression of INO1 expression","authors":"Chisom J. Onu ,&nbsp;Michael Adu ,&nbsp;Gil-Soo Han ,&nbsp;George M. Carman ,&nbsp;Miriam L. Greenberg","doi":"10.1016/j.bbalip.2026.159717","DOIUrl":"10.1016/j.bbalip.2026.159717","url":null,"abstract":"<div><div>Valproic acid (VPA) is a widely prescribed mood stabilizer used in the pharmacological management of bipolar disorder (BD), a psychiatric illness that affects 2% of the world's population. Although VPA has been in use for four decades, the therapeutic mechanism of action has not been determined. Inositol depletion is a proposed mechanism, but how VPA depletes inositol is not understood. Using the yeast model, in which the inositol biosynthetic pathway has been well characterized, we show that VPA supplementation leads to decreased levels of phosphatidic acid (PA), including decreased PA species 34:1. Supplementation with PA 34:1 or increasing PA levels by deletion of <em>PAH1</em> partially rescued VPA-induced repression of <em>INO1</em>. VPA-mediated repression is mediated by the Opi1-Ino2 interaction, as <em>INO1</em> expression is not repressed in an Ino2 mutant that does not bind to Opi1. The central role of PA in VPA-mediated repression has implications for the mechanism of action of VPA in mammalian cells.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 2","pages":"Article 159717"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A retrospective on phosphatidylinositol transfer proteins (PITPs) – A fifty-year journey","authors":"Shamshad Cockcroft","doi":"10.1016/j.bbalip.2025.159714","DOIUrl":"10.1016/j.bbalip.2025.159714","url":null,"abstract":"<div><div>This retrospective traces the evolution of our understanding of the phosphatidylinositol transfer protein (PITP) family over the past fifty years, beginning with its purification. I summarise the early identification of PITPs as phosphatidylinositol/phosphatidylcholine (PI/PC) transfer proteins and describe how the conserved PITP domain was subsequently recognised in five mammalian proteins, occurring either as a single domain or within a multi-domain architecture. Parallel genetic studies in <em>Drosophila</em> led to the discovery of RdgB, a retinal degeneration mutant protein containing a PITP domain. Later work revealed that some members of the PITP family members mediate PI/PA (phosphatidate) exchange enabling the reciprocal transfer of PA and PI during phospholipase C (PLC) signalling. PITPs thus function as key lipid exchangers, delivering PI for synthesis of phosphorylated derivatives including phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P₂) across cellular compartments. These activities position PITPs at the core of fundamental processes such as PLC signalling and Golgi membrane trafficking, where phosphoinositides play central regulatory roles. Finally, I highlight how PITPs have emerged as critical factors in diverse physiological processes and as contributors to a growing range of pathological conditions.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 2","pages":"Article 159714"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145800165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}