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

{"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}

{"title":"1H NMR studies of alterations in lipoprotein profiles in women diagnosed with gestational diabetes mellitus (GDM) and after delivery","authors":"Izabela Burzynska-Pedziwiatr ,&nbsp;Malgorzata Bukowiecka-Matusiak ,&nbsp;Barbara Pacholczyk-Sienicka ,&nbsp;Katarzyna Cypryk ,&nbsp;Monika Zurawska-Klis ,&nbsp;Andrzej Zieleniak ,&nbsp;Lukasz Albrecht ,&nbsp;Lucyna A. Wozniak","doi":"10.1016/j.bbalip.2025.159713","DOIUrl":"10.1016/j.bbalip.2025.159713","url":null,"abstract":"<div><div>The lipid abnormalities are observed in pregnant women with normal glucose tolerance (NGT) and those diagnosed with gestational diabetes mellitus (GDM), but in the latter, they are intensified and may indicate underlying metabolic dysfunction that transiently manifests during pregnancy. Due to the complex relationship between lipid metabolism and glucose regulation, alterations in lipoproteins may act as preliminary biomarkers for the early detection and monitoring of GDM and postpartum changes.</div><div>In the current study, we performed a ¹H NMR analysis of plasma lipoproteins in the cohort comprising pregnant NGT women and those diagnosed with GDM at three critical time points: 24–28 gestation week and 3 and 12 months postpartum.</div><div>After assignment of lipoprotein-associated signals in NMR spectra, Partial Least Squares Discriminant Analysis (PLS-DA) revealed clear distinctions between NGT and GDM groups.</div><div>Correlation analysis revealed a moderate negative correlation of CH₃VLDL, a moderate positive correlations of CH₂CH₂C=C with 2 h-OGTT and 1 h-OGTT, and a significant negative correlation of CH₃VLDL, and a positive correlation of CH₂CH₂C=C were noted for HOMA IR.</div><div>At the 3-months mark, the concentrations of (CH₂)_n LDL, CH₂CH₂CH₂CO VLDL, all unsaturated lipids, and (CH=CH) LDL + VLDL, CH₂/CH₃ LDL + VLDL, and CH=CH/CH₃ LDL + VLDL were decreased, while the concentrations of (C18 VLDL, CH₃ LDL, CH₂CH₂C=C, CH₂C=C, CH₂CO, C=CCH₂C=C, choline N(CH₃)₃, glyceryl CH₂OCOR) were increased. The concentrations of selected fractions at the 1-year postpartum time point remained unchanged.</div><div>Our findings provide essential insights into lipoprotein dysregulation in GDM and underscore possible implications for early intervention and long-term metabolic risk reduction for maternal health.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 2","pages":"Article 159713"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755153","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":"MiR-432 mediates bidirectional regulation in the determination of adipocyte fate","authors":"Liming Tian ,&nbsp;Guan Wang ,&nbsp;Shuhong Zhang ,&nbsp;Zhaohua He ,&nbsp;Fangfang Zhao ,&nbsp;Menghan Chang ,&nbsp;Wei Han ,&nbsp;Dandan Ye ,&nbsp;Shaobin Li ,&nbsp;Guangli Yang","doi":"10.1016/j.bbalip.2026.159715","DOIUrl":"10.1016/j.bbalip.2026.159715","url":null,"abstract":"<div><div>Fat deposition represents a fundamental physiological process in mammalian energy metabolism, yet its molecular regulatory mechanisms remain incompletely understood. Adipocytes, the primary site of fat storage, develop through proliferation and differentiation of preadipocytes—a process controlled by multiple molecular regulators. MicroRNAs (miRNAs) act as crucial post-transcriptional regulators and play an essential role in mammalian adipogenesis. However, their specific functions in ovine tail fat deposition remain poorly characterized. This study aimed to systematically investigate the regulatory role of miR-432 in adipogenesis using sheep tail fat as a model system. Through establishing an in vitro preadipocyte culture model and implementing gain- and loss-of-function approaches via miRNA overexpression and antisense oligonucleotide inhibition, we demonstrated that elevated expression of miR-432 significantly enhanced preadipocyte proliferation, accompanied by upregulation of proliferation-related genes (<em>Cyclin D</em>, <em>PCNA</em>). However, it decreased lipid droplet accumulation and reduced the expression of differentiation markers (<em>PPARγ</em>, <em>FABP4</em>). Conversely, inhibition of miR-432 reduced cellular proliferation, downregulated key cell cycle genes (<em>CCNB1</em>, <em>Cyclin B3</em>), and enhanced adipogenic differentiation, as evidenced by increased lipid droplet formation and elevated expression of adipogenic genes (<em>PPARγ</em>, <em>Adiponectin</em>, <em>FABP4</em>). These findings demonstrate that miR-432 exerts a dual regulatory role in sheep tail adipogenesis by modulating both proliferative and differentiative processes in adipocytes. This research provides novel molecular insights into the regulatory mechanisms underlying fat deposition.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 2","pages":"Article 159715"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917025","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":"The endocannabinoid-derived prostaglandin glycerol esters and prostaglandin ethanolamides modulate intestinal epithelial hallmarks of colitis","authors":"Joan Bestard-Escalas ,&nbsp;Olivia Sasportes ,&nbsp;Hafsa Ameraoui ,&nbsp;Mar González-Nicolau ,&nbsp;Mireille Alhouayek ,&nbsp;Giulio G. Muccioli","doi":"10.1016/j.bbalip.2026.159719","DOIUrl":"10.1016/j.bbalip.2026.159719","url":null,"abstract":"<div><div>Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract with a high impact on patients' quality of life.</div><div>The endocannabinoids 2-arachidonoylglycerol (2-AG) and <em>N</em>-arachidonoylethanolamine (AEA) are important modulators of inflammation. Their metabolism by cyclooxygenase (COX)-2 produces prostaglandin glycerol esters (PG-Gs) and prostaglandin ethanolamides (PG-EAs) that are endogenous analogues of the arachidonic acid-derived prostaglandins. Several PG-G and PG-EA possess interesting biological properties, notably in the context of colitis as we reported for PGD₂-G. However, while the properties of prostaglandins (such as PGE₂) on epithelial cells in the context of colon inflammation are well described, the biological effects of PG-Gs and PG-EAs are unknown.</div><div>Here we used Caco-2 spheroids and mouse colon organoids to evaluate how PG-Gs and PG-EAs modulate three epithelial hallmarks of colitis, namely the epithelial barrier integrity, the production of cytokines, and the wound healing process. Importantly, we tested the corresponding prostaglandins in parallel.</div><div>When analyzing the effects of these prostanoids on the production of pro-inflammatory cytokines, we found that PGD₂-G did decrease the production of TNFα and MCP-1 in activated Caco-2 spheroids. On colon organoids, PGE₂-G modulated the levels of TNFα, MIP2α, and KC and improved the survival of colon organoids in a DSS-plating efficiency assay without affecting stem cell dynamics. Our results put forth differential effects for PG-Gs, PG-EAs and the corresponding prostaglandins, and suggest that PGE₂-G could be an interesting lipid mediator in the context of colon epithelium inflammation.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 2","pages":"Article 159719"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958600","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":"MiR-424-3p suppresses adipogenesis via HNRNPA0 targeting and p53-mediated ferroptosis","authors":"Meng Li ,&nbsp;Yuqi Ye ,&nbsp;Shasha Lin ,&nbsp;Hanchen Jiang ,&nbsp;Dawei Zhang ,&nbsp;Jin Zhang","doi":"10.1016/j.bbalip.2025.159712","DOIUrl":"10.1016/j.bbalip.2025.159712","url":null,"abstract":"<div><div>MicroRNAs (miRNAs), a class of non-coding small RNAs, play critical roles in regulating adipocyte biology, including differentiation, proliferation, and lipid metabolism. This study investigates the role of miR-424-3p in adipogenesis. MiR-424-3p expression is dynamically upregulated during adipocyte differentiation. Functional analyses demonstrate that miR-424-3p overexpression suppresses lipid droplet accumulation and coordinately inhibits both anabolic (PPARγ, C/EBPα) and catabolic (ATGL, HSL) pathways; these effects are reversed by co-treatment with a miR-424-3p inhibitor. Lipidomic analysis reveals that miR-424-3p mediates membrane phospholipid remodeling, with significant changes predominantly in glycerophospholipids and sphingolipids, among which PE, PC, and LPE are the major affected species. Together with pathway enrichment analysis, increased lipid reactive oxygen species (ROS) levels, decreased glutathione (GSH) levels, and unaltered cell viability, these results collectively indicate that miR-424-3p may trigger ferroptosis signaling. Mechanistically, we demonstrate that miR-424-3p targets HNRNPA0, thereby upregulating p53 and suppressing ferroptosis inhibitors (SLC7A11, GPX4). HNRNPA0 overexpression reverses these phenotypes, restoring adipocyte metabolism and lipid storage capacity. Our findings establish miR-424-3p as an epigenetic regulator of adipose homeostasis via the HNRNPA0-p53-ferroptosis axis, which constrains lipid accumulation in 3T3-L1 cells. The evolutionary conservation of this mechanism across lipogenically active species highlights its potential as a therapeutic target for obesity-related metabolic disorders.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 2","pages":"Article 159712"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740748","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":"Curcumol ameliorates high-fat diet-induced hepatic fibrosis via dual regulation of FXR-CREB and Rab18-mediated hepatic stellate cell lipophagy","authors":"Na Wei ,&nbsp;Wanyu Feng ,&nbsp;Meijun Pan ,&nbsp;Xinyi Xu ,&nbsp;Shuguo Zheng ,&nbsp;Huanhuan Jin","doi":"10.1016/j.bbalip.2025.159710","DOIUrl":"10.1016/j.bbalip.2025.159710","url":null,"abstract":"<div><div>Curcumol, a bioactive constituent derived from <em>Rhizoma Curcumae</em> roots, possesses anti-inflammatory and anti-viral properties. This study investigated its therapeutic effects on lipophagy in hepatic stellate cells (HSCs) and lipid accumulation in hepatocytes within a model of high-fat diet-induced hepatic fibrosis, along with the underlying molecular mechanisms. Initially, curcumol treatment significantly attenuated lipid droplets (LDs) degradation and suppressed HSC activation, effects potentially associated with the inhibition of lipophagy. These outcomes were partially reversed by Rab18 overexpression, which modulates the autophagy-lysosomal pathway. Moreover, the ameliorative effect of curcumol on choline-deficient, L-amino acid-defined, 45 % high-fat diet (CDAHFD)-induced hepatic pathology was partially abolished upon Rab18 overexpression in mice. Importantly, curcumol promoted Farnesoid X receptor (FXR) expression, which inhibited the CREB/TORC2 interaction, thereby further suppressing LC3B expression and activation in LX2 cells. Additionally, curcumol impeded LD expansion and reduced lipid accumulation in palmitic acid (PA)-treated BNL-CL.2 cells and hepatocytes from CDAHFD-fed mice by inhibiting LD–endoplasmic reticulum (ER) contact formation, which could be reversed by Rab18 overexpression. In conclusion, curcumol inhibits HSC lipophagy by downregulating Rab18-mediated LD–autophagosome formation and enhancing the FXR–CREB interaction. Furthermore, it ameliorates hepatocyte lipid accumulation in fibrotic livers by disrupting Rab18-dependent LD–ER contacts. These findings underscore the therapeutic potential of curcumol in the treatment of HFD-induced hepatic fibrosis.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 2","pages":"Article 159710"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145751467","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":"Subcellular Cartography of the Phosphoinositide Multiverse","authors":"Morgan M.C. Ricci ,&nbsp;Claire C. Weckerly ,&nbsp;Gerald R.V. Hammond","doi":"10.1016/j.bbalip.2025.159706","DOIUrl":"10.1016/j.bbalip.2025.159706","url":null,"abstract":"<div><div>Phosphoinositides (PPIn) are low-abundance phospholipids that define membrane identity and direct compartment-specific signaling across eukaryotic cells. Marking fifty years since Michell's seminal 1975 review, we re-evaluate how the subcellular localization of these lipids informs their function. Using a historical and mechanistic framework, we survey evidence for the steady-state distribution of all eight PPIn species and their key precursor, phosphatidic acid, emphasizing live-cell biosensor studies and kinase localization. We conclude that PI(4,5)P₂ and PIP₃ signaling remain largely confined to the plasma membrane, whereas PI4P and PI3P occupy distinct but complementary domains of the Golgi and endosomal systems, and PI(3,5)P₂ marks specialized late endosomal compartments. Together, these patterns reveal PPIn as spatial rather than purely temporal signaling molecules—an ATP-derived currency maintaining the ordered heterogeneity of eukaryotic membranes. Understanding how these pathways self-regulate will define the next generation of phosphoinositide biology.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 2","pages":"Article 159706"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548097","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":"Roles in physiology and disease of the inositol phosphatase synaptojanin 1","authors":"Pietro De Camilli","doi":"10.1016/j.bbalip.2025.159708","DOIUrl":"10.1016/j.bbalip.2025.159708","url":null,"abstract":"<div><div>Synaptojanin 1 (Synj1) is a protein highly enriched in the nervous system which comprises tandemly arranged inositol 4-phosphatase and 5-phosphatase domains. Since its discovery as a synaptically enriched binding partner of SH3 domain containing proteins, Synj1 has been shown to be a key player in synaptic vesicle recycling via its property to couple the endocytic reaction to dephosphorylation of PI(4,5)P₂, a determinant of plasma membrane identity. Beyond its well established role in synaptic vesicle traffic, Synj1 has housekeeping roles at the interface of endocytosis, receptor signaling and regulation of actin nucleation. It is essential for postnatal life, while partial loss-of-function mutations are responsible for early-onset Parkinsonism and epilepsy. Conversely Synj1 overexpression, such as due to gene duplication in Down syndrome, may also have a pathogenic role. Here I review current knowledge about Synj1's molecular and physiological functions and the role of its dysfunction in disease.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1871 2","pages":"Article 159708"},"PeriodicalIF":3.3,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660148","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}