BBA Advances最新文献

{"title":"AGTRAP mediates exosome-driven communication between cancer cells and macrophages via p38 MAPK pathway to promote hepatocellular carcinoma.","authors":"Shanshan Liu, Zhenghang Li, Hongqing Liu, Xinyu Chen, Yilin Liu, Jun Tang, Yanlin Chen, Dan Zeng","doi":"10.1016/j.bbadva.2026.100189","DOIUrl":"https://doi.org/10.1016/j.bbadva.2026.100189","url":null,"abstract":"<p><strong>Background: </strong>Angiotensin II Receptor-Associated Protein (AGTRAP) is markedly overexpressed in hepatocellular carcinoma (HCC) cases associated with poor prognosis; however, its precise functional role remains inadequately elucidated.</p><p><strong>Objective: </strong>This study aimed to elucidate the functional role of AGTRAP in HCC progression and its impact on the tumor microenvironment (TME).</p><p><strong>Methods: </strong>We knocked down AGTRAP expression in HCC cell lines (HepG2 and SK-hep1) using shRNA and evaluated the impact of AGTRAP knockdown on hepatocellular carcinoma cells through proliferation, invasion, and migration. Immunofluorescence staining was used to analyze the distribution of M1-type and M2-type macrophages in HCC patient tissues. The signaling pathway mechanism by which AGTRAP regulates macrophage polarization was further analyzed, focusing on the p38 MAPK pathway. The effects and mechanisms of exosomes derived from AGTRAP-knockdown HCC cells on macrophage polarization were investigated.</p><p><strong>Results: </strong>Silencing AGTRAP significantly enhanced apoptosis, disrupted cell cycle progression, and diminished the invasive and migratory capacities of HCC cells.Tumors with high AGTRAP expression exhibited increased M2-type macrophages and decreased M1-type macrophages, indicating a shift in the TME towards an immunosuppressive state.Mechanistic studies revealed that AGTRAP modulates macrophage polarization by interacting with the p38 MAPK signaling pathway.Exosomes derived from AGTRAP-silenced HCC cells also influenced macrophage polarization via the p38 MAPK pathway.</p><p><strong>Conclusion: </strong>AGTRAP facilitates HCC progression by mediating exosomal communication between cancer cells and macrophages via the p38 MAPK pathway, underscoring its pivotal role in shaping the immunosuppressive tumor microenvironment.</p>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"9 ","pages":"100189"},"PeriodicalIF":3.0,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering a mechanistic basis for the pathological effect of the GNAO1 E246K variant in neurodevelopmental disorder","authors":"Isra Sadiya ,&nbsp;Irina Nekrasova ,&nbsp;Meirav Avital-Shacham ,&nbsp;Naomi van Wijk ,&nbsp;Keren Zohar ,&nbsp;Nir Kalisman ,&nbsp;Dina Shneidman-Duhovny ,&nbsp;Ehud Banne ,&nbsp;Andreea Nissenkorn ,&nbsp;Lubov Blumkin ,&nbsp;Michal Linial ,&nbsp;Mickey Kosloff","doi":"10.1016/j.bbadva.2026.100182","DOIUrl":"10.1016/j.bbadva.2026.100182","url":null,"abstract":"<div><div>Pathogenic variants in the GNAO1 gene, which encodes for Gα_o, a major neuronal G protein, are associated with neurodevelopmental disorders, epilepsy, and movement disorders. We identified and characterized in detail a de novo heterozygous GNAO1 E246K pathogenic variant in an Israeli female infant with complex developmental delay and substantial motor difficulties. This variant has been reported in other cases as a recurrent pathogenic variant in patients with motor dysfunction and a broad range of neurological outcomes. To investigate the molecular and functional consequences of the Gα_o E246K variant, we employed structural modeling and analysis, mass spectrometry-based proteomics, biochemical assays, and cellular functional assays. Our biochemical results show that this variant does not affect nucleotide binding, nor basal or RGS-accelerated GTP hydrolysis. Despite the E246 position location within a predicted effector binding region, mass spectrometry analysis did not identify any novel cellular partners. Instead, we demonstrate that the E246K variant disrupts the Gα_o regulatory GTPase cycle by directly impairing Gβγ dissociation. This impairment overrides the function of wild-type Gα_o, explaining the dominant effect and the severity of the neurogenetic phenotype despite a heterozygous background. These findings establish a new molecular mechanism for a GNAO1 variant with dominant-negative effects on the GTPase regulatory cycle. The insights gained from studying this mechanism of action provide a basis for developing specific and personalized therapeutic strategies based on the outcome of a missense mutation in GNAO1.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"9 ","pages":"Article 100182"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collateral lethality of NAD kinase in 1p36 deleted tumors drives vulnerability to NAD kinase 2 depletion","authors":"Saki Suyama-Banjo,&nbsp;Kengo Watanabe,&nbsp;Hirokazu Ishikawa,&nbsp;Yohei Yoshihama,&nbsp;Yasuhide Hirota,&nbsp;Shinji Tsutsumi","doi":"10.1016/j.bbadva.2026.100192","DOIUrl":"10.1016/j.bbadva.2026.100192","url":null,"abstract":"<div><div>The deletion of tumor suppressor genes often occurs in a tumor-specific manner and is accompanied by the unintended loss of adjacent genes. Nicotinamide adenine dinucleotide kinase (<em>NADK</em>), located at a tumor suppressive locus on chromosome 1p36, plays a pivotal role in the biosynthesis of NADP and NADPH and has a closely related paralog, <em>NADK2</em>, in human cells. Although synthetic lethality between NAD kinases was reported in yeast, the relationship between <em>NADK</em> and <em>NADK2</em> in human cells remains unclear. Here, we investigated alterations of the <em>NADK</em> gene expression across various tumor types and assessed whether there is a synthetic lethal relationship between these NAD kinases in human cells. Analysis of The Cancer Genome Atlas dataset revealed <em>NADK</em> gene deletion in multiple tumor types. Depletion of both <em>NADK</em> and <em>NADK2</em> using siRNA decreased cellular NADP(H) levels and inhibited cell proliferation, resulting in the induction of apoptosis. Notably, <em>NADK2</em> knockdown alone markedly impaired cell proliferation and NADP(H) production in <em>NADK</em> homozygous-deleted tumor cells, and also reduced proliferation in <em>NADK</em> heterozygous-deleted tumor cells, whereas in <em>NADK</em>-intact tumor cells only de novo NADP synthesis, but not its intracellular levels or proliferation, was affected. These findings suggest that loss of the <em>NADK</em> gene in tumor cells confers vulnerability to <em>NADK2</em> depletion.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"9 ","pages":"Article 100192"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147802422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hidden faces of alpha-synuclein: Cryo-EM revelation of fibril polymorphs driven by disease, mutations, and PTMs","authors":"Mitra Pirhaghi ,&nbsp;Fatemeh Mamashli ,&nbsp;Bagher Davaeil ,&nbsp;Mahya Mohammad-Zaheri ,&nbsp;Zahra Mousavi-Jarrahi ,&nbsp;Jörg Tatzelt ,&nbsp;Ali Akbar Saboury","doi":"10.1016/j.bbadva.2025.100179","DOIUrl":"10.1016/j.bbadva.2025.100179","url":null,"abstract":"<div><div>Alpha-synuclein (α-Syn) is a neuronal protein implicated in the pathogenesis of several neurodegenerative disorders collectively known as synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. This article provides a comprehensive overview of the structural characteristics of α-Syn, emphasizing its fibrillar aggregation and the resulting polymorphic fibril forms. Using advances in cryo-electron microscopy, a diverse range of α-Syn fibril polymorphs has been elucidated, both from <em>in vitro</em> preparations and patient-derived brain samples. We further explore the impact of mutation and post-translational modifications—such as truncation and phosphorylation —on α-Syn structure and the unique polymorphs they induce. The article underscores the biological and pathological relevance of α-Syn polymorphism, highlighting how different structural strains may underlie the structural and pathological heterogeneity observed in synucleinopathies. Understanding the mechanisms driving polymorph formation is critical for deciphering disease progression and developing targeted therapeutic strategies.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"9 ","pages":"Article 100179"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145938443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF-β2/OPTN/FOXC1/miR-200 axis regulates actin dynamics in human trabecular meshwork cells","authors":"Chenna Kesavulu Sugali ,&nbsp;Navya Naidu Gajula ,&nbsp;Suresh Chava ,&nbsp;Aramati Bindu Madhava Reddy","doi":"10.1016/j.bbadva.2025.100177","DOIUrl":"10.1016/j.bbadva.2025.100177","url":null,"abstract":"<div><div>Glaucoma is the second leading cause of irreversible blindness globally, with elevated intraocular pressure (IOP) being its primary risk factor. Current therapeutic approaches, such as beta-blockers, alpha-adrenergic agonists, Rho-kinase inhibitors, etc., aim to reduce IOP levels. However, the molecular mechanisms underlying altered IOP remain poorly understood. In this study, we have treated primary human trabecular meshwork cells (HTM) with exogenous dexamethasone (dex) or transforming growth factor beta-2 (TGF-β2) to investigate their effects on glaucoma candidate genes. Interestingly, our findings reveal that FOXC1 acts as a repressor of <em>CYP1B1</em>, and optineurin (OPTN) facilitates the ubiquitination of FOXC1, thereby inducing the expression of CYP1B1. Furthermore, we found that the <em>miR-200</em> family and other miRNAs regulate these glaucoma candidate genes. Furthermore, TGF-β2 downregulates the <em>miR-200</em> family, whereas the <em>miR-200</em> family targets <em>FOXC1</em>, exerting reversible effects by altering the extracellular matrix. Thus, modulating the TGF-β2/OPTN/FOXC1/<em>miR-200</em> axis appears critical in regulating actin dynamics in the anterior eye segment.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"9 ","pages":"Article 100177"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural modification of 5-alkyl-4-phenyl-thiazole-based fatty acid amide hydrolase and soluble epoxide hydrolase inhibitors to alleviate orofacial inflammatory pain in the rat","authors":"Gabrielle Gorostiza ,&nbsp;Madison Mercado ,&nbsp;Lucy Pavana ,&nbsp;Daniel Carr ,&nbsp;Cassandra Yuan ,&nbsp;Amanda Tsang ,&nbsp;Karen Gomez ,&nbsp;Ian Minton ,&nbsp;Dylan Carrillo ,&nbsp;Manuel Berumen ,&nbsp;Stevan Pecic ,&nbsp;Ram Kandasamy","doi":"10.1016/j.bbadva.2026.100191","DOIUrl":"10.1016/j.bbadva.2026.100191","url":null,"abstract":"<div><div>Orofacial pain is difficult to manage. Treatments like nonsteroidal anti-inflammatory drugs (NSAIDs), and serotonin agonists provide limited relief or produce side effects. These limitations highlight the need for alternative strategies that reduce orofacial pain without adverse effects. One approach is polypharmacology, where a single compound modulates multiple targets involved in pain. Fatty acid amide hydrolase (FAAH) and soluble epoxide hydrolase (sEH) are regulators of pain that can be targeted simultaneously to enhance antinociceptive efficacy. We previously reported that the 4-phenylthiazole-based dual FAAH/sEH inhibitor <strong>SW-17</strong> does not alleviate acute orofacial pain in rats, and it showed low stability in rat liver microsomes. We introduced electronic and steric modifications to the thiazole and phenyl rings of the 4-phenylthiazole scaffold to improve the stability and better understand structure-activity relationship of this set of analogs. An 11-compound library was synthesized by varying alkyl groups at position 5 of the thiazole ring and substituents on the phenyl ring. Several analogs exhibited nanomolar potency at both enzymes. The most potent compound, <strong>4j</strong>, exhibited IC₅₀ values of 18.7 nM and 25.1 nM for human FAAH and sEH, respectively. <strong>4j</strong> was evaluated in rat liver microsomes where it exhibited relatively low metabolic stability but better than <strong>SW-17</strong>. ADMET studies indicated that <strong>4j</strong> possesses promising safety features. At 3 mg/kg, <strong>4j</strong> reversed acute orofacial inflammatory pain, whereas <strong>SW-17</strong> was ineffective. This effect was comparable to sumatriptan and did not reduce voluntary wheel running. These findings imply that optimized dual FAAH/sEH inhibitors can alleviate orofacial pain without affecting normal behavior.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"9 ","pages":"Article 100191"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147749107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitors of phosphodiesterase 1 enhance paclitaxel cytotoxicity in a MDA-MB-231-derived cell line by promoting microtubule stabilization","authors":"Hsiao-Hui Kuo,&nbsp;Chien-Wei Huang,&nbsp;Tsai-Ming Lu,&nbsp;Wei-Rou Chiang,&nbsp;Ling-Huei Yih","doi":"10.1016/j.bbadva.2026.100187","DOIUrl":"10.1016/j.bbadva.2026.100187","url":null,"abstract":"<div><div>Resistance of tumor cells to chemotherapy remains a critical obstacle to effective cancer treatment. Although paclitaxel is one of the most commonly used chemotherapeutic agents for treating triple-negative breast cancer (TNBC), the mechanisms underlying paclitaxel resistance are not fully understood. We previously found that phosphodiesterase 1C (PDE1C) was substantially upregulated in a paclitaxel-resistant T50RN cell clone established from the human TNBC cell line MDA-MD-231. In this study, we aimed to explore whether and how PDE1C modulates resistance to paclitaxel in T50RN cells. Our results showed that depletion of PDE1C enhanced paclitaxel cytotoxicity, and that pharmacological inhibition of PDE1 potentiated paclitaxel-induced antiproliferative and antimitotic effects in T50RN cells. Additionally, intracellular cyclic adenosine monophosphate (cAMP) levels were lower in T50RN cells than in parental MDA-MB-231 cells. PDE1 inhibition restored the cAMP level, suggesting that cAMP-degrading activity of PDE1 is elevated in the T50RN cells. Similar to PDE1 inhibitors, the cell permeable cAMP analog 8‑bromo-cAMP or the adenylate cyclase activator forskolin increased cAMP levels and concurrently augmented paclitaxel-induced cytotoxicity and spindle abnormalities in T50RN cells. Furthermore, PDE1 inhibitors, forskolin, and an agonist of the cAMP downstream effector EPAC enhanced paclitaxel-mediated microtubule (MT) stabilization. Thus, PDE1 inhibition may act through cAMP/EPAC signaling to facilitate MT stabilization and potentiate the antiproliferative and antimitotic effects of paclitaxel in T50RN cells. Upon PDE1 inhibition, paclitaxel-treated T50RN cells exhibited signs of endoplasmic reticulum (ER) stress and apoptosis. Together, our <em>in vitro</em> findings indicate that PDE1C overexpression contributes to paclitaxel resistance.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"9 ","pages":"Article 100187"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147656322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adjacent domains drive the emergence of misfolded intermediates in the folding pathway of the PDZ4 from MAGI1","authors":"Valeria Pennacchietti ,&nbsp;Cosmin Marian Obreja ,&nbsp;Dimitrios Marinidis ,&nbsp;Sara Di Matteo ,&nbsp;Rodolfo Ippoliti ,&nbsp;Stefano Gianni ,&nbsp;Francesca Malagrinò","doi":"10.1016/j.bbadva.2026.100184","DOIUrl":"10.1016/j.bbadva.2026.100184","url":null,"abstract":"<div><div>Protein misfolding in multidomain assemblies emerges from a complex interplay between intra- and interdomain interactions. Here, we dissect how neighboring domains shape the folding and misfolding of the PDZ4 domain from the scaffold protein MAGI1. Exploiting the single intrinsic tryptophan in PDZ4, we monitored its behavior in the isolated domain, in the PDZ3–4 tandem, and within the five-domain PDZ2–6 supramodule by equilibrium and kinetic (un)folding experiments over a broad pH range. Equilibrium denaturation reveals that PDZ4 displays a cooperative, two-state-like transition with similar thermodynamic stability in all constructs, indicating that domain adjacency does not appreciably affect its native state. In contrast, kinetic measurements uncover pronounced deviations from two-state behavior. PDZ4 alone populates a transient intermediate, whose population and associated kinetic slowdown are markedly amplified in the tandem and even more in the supramodular context, consistent with the formation of a misfolded ensembles stabilized by non-native interdomain contacts. Acidic pH selectively enhances the kinetic trap in PDZ3–4 and PDZ2–6, but not in PDZ4 alone, pointing to a key role of electrostatics at interdomain interfaces, potentially involving specific salt bridges. Structural inspection suggests the presence of potential specific salt bridges (Asp871/Glu901 with Arg873/Lys905), although further investigation is required. Our data show that misfolding of MAGI1 PDZ4 is a context-dependent, cooperative property of adjacent domains rather than a simple by-product of folding, and illustrate how supramodular organization encodes kinetic plasticity in scaffold proteins.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"9 ","pages":"Article 100184"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147395490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactive derivatives of the antimicrobial peptide esculentin-1a promote human dermal fibroblast migration and activate genes involved in early wound healing","authors":"Floriana Cappiello ,&nbsp;Eleonora Grisard ,&nbsp;Alice Traversa ,&nbsp;Danilo Ranieri ,&nbsp;Maria Luisa Mangoni","doi":"10.1016/j.bbadva.2026.100186","DOIUrl":"10.1016/j.bbadva.2026.100186","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) are essential components of the innate immune system and have emerged as promising candidates against antibiotic-resistant infections. Beyond their antimicrobial activity, AMPs also play a crucial role in regulating tissue regeneration processes, including wound healing. Previous studies have shown that the frog skin-derived AMP, esculentin-1a(1-21) [Esc(1-21)], promotes wound healing by accelerating keratinocyte migration. Its derivative, esculentin-1a(1-21)-1c [Esc(1-21)-1c] has proven even more effective in facilitating wound closure in alveolar and bronchial epithelial cell monolayers. Given the essential role of dermal fibroblasts in skin regeneration, this study aimed to investigate the effects of Esc(1-21) and its two derivatives, Esc(1-21)-1c and [Aib⁸]-Esc(1-21) (containing the non-natural α-aminoisobutyric acid at position 8), on the activation of human primary dermal fibroblasts (hDFs) during the healing of a pseudo-wound. The results demonstrated that all three peptides significantly enhanced hDFs migration and stimulated wound closure by activating the MAPK/ERK signaling pathway, without affecting cell proliferation. Importantly, for Esc(1-21) and [Aib⁸]-Esc(1-21), this activation was clearly mediated by Epidermal Growth Factor Receptor (EGFR). Finally, the peptides upregulated the expression of early wound healing markers, such as Collagen I and Collagen III, but did not alter the expression of late-stage markers, including MMP9 and α-SMA. These findings highlight the regenerative potential of Esc(1-21) and its derivatives and suggest their relevance in therapeutic strategies for impaired wound healing.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"9 ","pages":"Article 100186"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147612145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thermodynamic signatures in ß-oxidation drive selective mobilization of fatty acids during negative energy balance in white adipose tissues","authors":"Natarajan Ganesan","doi":"10.1016/j.bbadva.2026.100181","DOIUrl":"10.1016/j.bbadva.2026.100181","url":null,"abstract":"<div><div>A theoretical model of mitochondrial β-oxidation efficiency is presented, using ATP yield per oxygen atom (P:O_β-ox) as a proxy for performance under oxygen-limited conditions. Expressed as a function of chain length and unsaturation, the model generates hyperbolic efficiency surfaces whose maxima mirrors the natural abundance of fatty acids in adipose tissues. It predicts a crossover near <em>d</em> ≈ 1.6, where efficiency becomes chain-length–independent—thus matching the dominance of monounsaturated FAs in mammals. The model aligns with empirical mobilization patterns and suggests an oxygen- and ATP-sensitive regulatory axis shaping lipid profiles in hypoxic or energy-stressed states.</div></div>","PeriodicalId":34672,"journal":{"name":"BBA Advances","volume":"9 ","pages":"Article 100181"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146188279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}