bims-toxgon 2026-02-15 papers

bims-toxgon

Biomed News

on Toxoplasma gondii metabolism

Issue of 2026–02–15
25 papers selected by
Lakesh Kumar, BITS Pilani

Structural and regulatory principles underlying apicomplexan conoid function.
Host kynurenine monooxygenase (KMO) serves as a critical immune defense factor restricting Toxoplasma gondii proliferation.
The role of TgEfhc3 in Toxoplasma gondii biology and its prospects as a subunit vaccine.
Antiproliferative Plaque Assay for Screening in vitro Bioactive Molecules against Toxoplasma gondii Tachyzoites.
Protocol to enhance pre-sexual and sexual differentiation of Toxoplasma gondii using retinal cells and intestinal organoid-derived monolayers.
Mechanistic understanding of the protective effects of baicalein against the inflammatory response induced by Toxoplasma gondii in Ana-1 macrophages.
Inhibition of Histone Lysine Acetyltransferases by Coenzyme A Analogs.
A Proteomic Study of the Dual Oncogenic and Tumor-Suppressive Roles of SIRT3 in Lung and Breast Cancer Cell Lines.
SIRT2 versus Lck.
Novel high-resolution ion mobility mass spectrometry for site-specific quantification of the sirtuin-5 regulated kidney succinylome.
Effects of Toxoplasma Gondii Type II Infection on Serum Serotonin Concentration and Indoleamine 2,3-Dioxygenase Gene Expression in Balb/c Mice.
F26BP enables control of glycolysis rate independent of energy state.
PTMOverlay: A Proteomic Tool to Visualize Post-Translational Modifications Across Evolution.
Genome-wide identification and expression profiling of the histone deacetylase gene family in Fusarium oxysporum.
Mitochondrial ribosomes in apicomplexan and trypanosomatid parasites: Dissimilar drivers of complexity and convergent features.
Adrenergic signaling during parasitic infections.
The Glutamine-α-Ketoglutarate Metabolic Axis Controls Vascular Smooth Muscle Cell Function.
The role and mechanism of histone deacetylase in COPD.
Mining lysine post-translational modification sites by integrating protein language model representations with structural context.
Scaffolding of the H4K5ac chromatin remodeling complex by lncRNA MAHAC mediates epithelial-mesenchymal transition.
Lysine malonylation regulates human sperm motility.
[Regulatory effects and mechanisms of protein post-translational modifications on BK channel in metabolic syndrome-related diseases].
Subcellular Redistribution of Endomembrane GPR15 Promotes NAD+-Mediated Metabolic Reprogramming and Boosts 5-FU Chemosensitivity in Colorectal Cancer.
Lipid droplets and major metabolic disorders.
Isocitrate Dehydrogenase Inhibitors in Acute Myeloid Leukemia.

Trends Parasitol. 2026 Feb 06. pii: S1471-4922(26)00002-4. [Epub ahead of print]

Structural and regulatory principles underlying apicomplexan conoid function.

Albert Tell I Puig, Dominique Soldati-Favre.

  Zeng et al. and Qian et al. reveal in their cryogenic electron microscopy (cryo-EM) studies how apicomplexan parasites extensively remodel tubulin to construct the conoid, a specialized invasion organelle. Distinct microtubule assemblies integrate mechanical support, force generation, and secretion control, providing a structural framework that underpins parasite motility and host cell entry.

Keywords:  Toxoplasma gondii; conoid fibers; invasion; microtubules; motility; preconoidal rings

DOI:  https://doi.org/10.1016/j.pt.2026.01.002
Acta Trop. 2026 Feb 06. pii: S0001-706X(26)00046-X. [Epub ahead of print]275 108012

Host kynurenine monooxygenase (KMO) serves as a critical immune defense factor restricting Toxoplasma gondii proliferation.

Sheng-Jie Tang, Zhong-Yang Chen, Ya-Fei Song, Yanlong Gu, Yanmin You, Dong-Hui Zhou.

  Toxoplasma gondii is an obligate intracellular protozoan parasite capable of infecting virtually all warm-blooded animals. The kynurenine pathway (KP), a key route of tryptophan catabolism, serves as a critical immunometabolic checkpoint in cancer, autoimmune disorders, and neurodegenerative diseases. Although the kynurenine monooxygenase (KMO)-derived metabolite quinolinic acid (QUIN) has well-documented antiviral effects, its role in antiparasitic immunity remains unexplored. Here, we identify KMO as a critical mediator of host defense against T. gondii. Upon infection, T. gondii significantly suppresses host KMO expression along with its downstream metabolites, including 3-hydroxykynurenine (3-HK) and QUIN. Functional studies in Vero cells demonstrate that KMO overexpression effectively restricts parasite proliferation, whereas RNA interference (RNAi)-mediated knockdown (KD) of KMO increases parasite burden. Collectively, these findings establish KMO as a non-canonical determinant of anti-T. gondii immunity and nominate KP potentiation as a therapeutic strategy for toxoplasmosis.

Keywords:  Antiparasitic immunity; Host-pathogen interactions; Kynurenine 3-monooxygenase (KMO); Kynurenine pathway; Toxoplasma gondii

DOI:  https://doi.org/10.1016/j.actatropica.2026.108012
Parasit Vectors. 2026 Feb 11.

The role of TgEfhc3 in Toxoplasma gondii biology and its prospects as a subunit vaccine.

Xiaowei Tian, Hangbin Ma, Qiangqiang Wang, Boya Zhu, Yajing Li, Jing Zhang, Jinghui Wang, Yina Hu, Yun Li, Zhenchao Zhang, Zhenke Yang, Xuefang Mei, Shuai Wang.

   BACKGROUND: Toxoplasmosis, caused by Toxoplasma gondii, poses a significant global health threat, with no commercial vaccine available for humans. The parasite's egress process, which bridges its intracellular replication cycles and is critical for survival and dissemination, is tightly regulated by calcium. Notably, the T. gondii EF-hand domain-containing protein (Efhc) exhibits the highest Ca2⁺-binding affinity among its calcium-binding proteins.
METHODS: CRISPR/Cas9 was used to generate a conditional knockout strain (TgEfhc3-C-AID). Phenotypic assays (plaque, intracellular proliferation, egress, invasion and murine virulence) were used to assess its impact on tachyzoite growth and development. Subsequently, TgEfhc3 antigenicity was analyzed using DNAstar software, immunofluorescence assays and Western blots. Recombinant TgEfhc3 (rTgEfhc3) proteins, expressed in Escherichia coli, were subcutaneously administered to BALB/c mice to evaluate their protective efficacy against acute toxoplasmosis. Immune mechanisms induced by rTgEfhc3 were analyzed by measuring serum IgG/IgG subclasses (IgG1, IgG2a) and splenic T cell cytokines (IL-4, IFN-γ, IL-10) by ELISA and the the frequencies of CD4+ and CD8+ T cells by flow cytometry.
RESULTS: Genetic deletion severely impaired tachyzoite proliferation, egress and invasion, indicating that it is essential in T. gondii biology. Furthermore, recombinant TgEfhc3 was evaluated as a subunit vaccine in a mouse model and was subsequently shown to partially protect against acute T. gondii infection. Immunization induced high levels of anti-T. gondii IgG and subclasses, enhanced Th1/Th2 cytokine production (IL-4, IFN-γ, IL-10) in splenic T lymphocytes and stimulated robust CD4⁺ T-cell proliferation. This elicited complex cellular and humoral immunity significantly prolonged survival time following acute T. gondii infection.
CONCLUSIONS: This study found that TgEfhc3 is crucial for T. gondii tachyzoite growth and development, providing new insights into infection mechanisms. Given the partial protective immunity conferred, TgEfhc3 warrants consideration as a component in future toxoplasmosis vaccine strategies.

Keywords:   Toxoplasma gondii ; Biological function; CRISPR/Cas9; Immunoprotective effect; TgEfhc3

DOI:  https://doi.org/10.1186/s13071-026-07274-8
J Vis Exp. 2026 Jan 23.

Antiproliferative Plaque Assay for Screening in vitro Bioactive Molecules against Toxoplasma gondii Tachyzoites.

Mike Dos Santos, Andréia Luiza Oliveira Costa, Mariana Maciel Cunha, Adalberto Alves Pereira Filho, Ricardo Wagner de Almeida Vitor, Érica S Martins-Duarte.

Toxoplasmosis is a parasitic infection commonly related to ocular lesions and neonatal malformations. Since the early 1950s, the first-line treatment of this disease has relied on the combination of sulfadiazine, pyrimethamine, and folinic acid. Over those years, only a few alternative regimens have been introduced. This highlights the need for discovering new bioactive molecules against Toxoplasma gondii. Given that this pathogen is an obligate intracellular parasite, traditional drug screening in the laboratory typically requires expensive materials and equipment, such as assays using fluorescent proteins or β-galactosidase-expressing parasites. Additionally, methods like optical microscopy quantification can be time-consuming. The plaque assay is a method that evaluates the intensity of intracellular pathogen proliferation by measuring the number of regions and area of destruction in a cell monolayer damaged by the parasite's lytic cycle. This work describes an optimized plaque assay protocol designed for screening active molecules against intracellular tachyzoites of T. gondii in vitro. This protocol utilizes inexpensive materials and a straightforward laboratory setup, yielding rapid and reproducible results that facilitate the identification of new active molecules against this parasite by various research groups.

DOI: https://doi.org/10.3791/69725
STAR Protoc. 2026 Feb 11. pii: S2666-1667(26)00020-1. [Epub ahead of print]7(1): 104367

Protocol to enhance pre-sexual and sexual differentiation of Toxoplasma gondii using retinal cells and intestinal organoid-derived monolayers.

Saira Cancela, Florencia Sena, Romina Pagotto, María E Francia, Mariela Bollati-Fogolín.

  Toxoplasma gondii undergoes pre-sexual and sexual differentiation primarily in feline hosts, limiting experimental study. Here, we present a protocol for enhancing T. gondii stage differentiation using non-feline in vitro systems. We describe culturing human retinal pigment epithelial cells and murine intestinal organoid-derived monolayers in felid-environment-like with linoleic acid excess (FELIX) medium to mimic feline intestinal lipid biochemistry, combined with conditional MORC depletion to promote stage conversion. We detail procedures for host cell preparation, parasite culture, infection, and assessment of stage-specific gene and protein expression. For complete details on the use and execution of this protocol, please refer to Cancela et al.1.

Keywords:  Cell Biology; Metabolism; Microbiology; Microscopy; Model Organisms; Molecular Biology; Organoids

DOI:  https://doi.org/10.1016/j.xpro.2026.104367
Mol Immunol. 2026 Feb 09. pii: S0161-5890(26)00018-0. [Epub ahead of print]191 22-36

Mechanistic understanding of the protective effects of baicalein against the inflammatory response induced by Toxoplasma gondii in Ana-1 macrophages.

XiaoJuan Wang, ZhengQing Yu, WeiYu Qi, YuChen Jiang, PingLong Yang, JiuSu Tu, YunNan Fang, Pan Zhou, Li Zhang.

  Baicalein is an active flavonoid compound derived from Scutellaria baicalensis, a member of the Lamiaceae family, and has been widely reported to exhibit antioxidant, anti-inflammatory, and antimicrobial properties. However, the precise mechanisms underlying the anti-inflammatory effects of baicalein in Toxoplasma gondii infection-induced inflammation remain unclear. This study aims to systematically investigate the regulatory effects of baicalein on inflammation associated with T. gondii infection and its molecular mechanisms. The results indicate that baicalein significantly inhibits T. gondii proliferation, the production of inflammatory mediators and reduces the expression levels of pro-inflammatory cytokines. Further experiments revealed that baicalein effectively blocks the excessive activation of the cGAS-STING and NOD-like receptor signaling pathways in T. gondii-stimulated Ana-1 cells, thereby inhibiting the amplification of inflammatory signals. Additionally, baicalein enhances the expression of autophagy-related proteins, promoting autophagy and alleviating oxidative stress-induced cellular damage and inflammation. In conclusion, this study demonstrates that baicalein exerts its anti-inflammatory effects by activating autophagy and inhibiting the excessive activation of cGAS-STING and NOD-like receptor signaling pathways, effectively suppressing T. gondii infection-induced macrophage inflammation. These findings provide new theoretical insights into the potential therapeutic application of baicalein in infectious diseases.

Keywords:  Autophagy; Baicalein; CGAS-STING signaling pathway; Inflammation; NOD signaling pathway; Toxoplasma gondii

DOI:  https://doi.org/10.1016/j.molimm.2026.01.012
Molecules. 2026 Jan 29. pii: 477. [Epub ahead of print]31(3):

Inhibition of Histone Lysine Acetyltransferases by Coenzyme A Analogs.

Faidra Voukia, Nurgül Bilgin, Steffen Bundgaard Andersen, Jasmin Mecinović.

  Histone lysine acetylation is a widespread posttranslational modification, essential for vital functions in eukaryotic organisms. Histone lysine acetyltransferases (KATs) employ acetyl-coenzyme A as a universal acetyl donor for acetylation of lysine residues in histone and non-histone proteins. Despite the biomedicinal importance of modulation of the KAT activity, application of the acetyl-coenzyme A cosubstrate structure for the design of potent and selective inhibitors has been underexplored. Here, we developed functionalized coenzyme A analogs as inhibitors against human histone lysine acetyltransferases GCN5, KAT8, and HAT1. In contrast to the unmodified coenzyme A, which was found to be a poor inhibitor of GCN5 and KAT8 (IC50 > 150 μM), we showed that a ketone-substituted coenzyme A was the most potent inhibitor of GCN5 and KAT8 (IC50 = 10.9 μΜ and 13.6 μΜ, respectively). Coenzyme A and an acetamide-substituted coenzyme A efficiently inhibited HAT1 (IC50 = 7.3 μΜ and IC50 = 3.9 μΜ, respectively). Our work demonstrates that human KATs can be efficiently and selectively inhibited by S-functionalized coenzyme A, the results exhibiting significant potential towards development of highly active chemical probes for biomedically important KATs.

Keywords:  acetylation; coenzyme A; epigenetics; histone; lysine acetyltransferases

DOI:  https://doi.org/10.3390/molecules31030477
Int J Mol Sci. 2026 Jan 28. pii: 1325. [Epub ahead of print]27(3):

A Proteomic Study of the Dual Oncogenic and Tumor-Suppressive Roles of SIRT3 in Lung and Breast Cancer Cell Lines.

Marisol Ayala Reyes, Diana Lashidua Fernández Coto, Ramiro Alonso Bastida, György Marko-Varga, Jeovanis Gil, Sergio Encarnación-Guevara.

  Mitochondria play a crucial role in metabolism and energy production by generating adenosine triphosphate (ATP) through oxidative phosphorylation. They also help maintain intracellular calcium levels, facilitate communication between the nucleus and cytoplasm, detoxify reactive oxygen species (ROS), and regulate apoptosis. Reversible acetylation of mitochondrial proteins is a key post-translational modification influencing these processes, with the NAD+-dependent deacetylase SIRT3 being a major regulator. While SIRT3 has been described as a tumor suppressor in some contexts and as a tumor promoter in others, its role appears to be tissue- and metabolism-specific. Here, we compared the proteomic and acetylomic responses of lung adenocarcinoma (A549) and breast adenocarcinoma (MCF7) cell lines to SIRT3 inhibition by 3-TYP. The two lines were selected based on distinct metabolic phenotypes and reported differences in basal SIRT3 abundance. Total proteome and mitochondrial-enriched fractions were analyzed separately for each cell line to avoid cross-line normalization bias. We identified 6457 proteins and 4199 acetylated peptides, revealing distinct pathway enrichments and acetylation changes after SIRT3 inhibition. A549 cells showed increased oxidative metabolism, while MCF7 cells exhibited metabolic reprogramming. These results indicate that the proteomic impact of SIRT3 modulation is strongly influenced by cellular metabolic context. All raw mass spectrometry data are publicly available in PXD063181.

Keywords:  acetylation; cancer; metabolism; mitochondria; oxidative phosphorylation; post-translational modification; sirtuin

DOI:  https://doi.org/10.3390/ijms27031325
Sci Signal. 2026 Feb 10. 19(924): eaeg1336

SIRT2 versus Lck.

John F Foley.

Inhibiting the deacetylase SIRT2 increases the activity of the kinase Lck to enhance T cell receptor signaling.

DOI: https://doi.org/10.1126/scisignal.aeg1336
J Proteomics. 2026 Feb 11. pii: S1874-3919(26)00028-X. [Epub ahead of print] 105625

Novel high-resolution ion mobility mass spectrometry for site-specific quantification of the sirtuin-5 regulated kidney succinylome.

Birgit Schilling, Leonard Rorrer, Lauren Royer, Anne Silva-Barbosa, Katherine Pfister, Eric Goetzman, Sunder Sims-Lucas, Daniel DeBord, Joanna Bons.

  Protein post-translational modifications (PTMs) dynamically regulate essential biological and cellular processes. Lysine succinylation changes the amino acid charge, potentially affecting protein structures and functions, and dysregulation of protein succinylation may lead to metabolic disorders. Proteome-wide succinylation quantification using proteomic tools remains challenging, especially due to the low abundance of succinylated peptides and the frequent presence of isomeric PTM forms. Ion mobility spectrometry workflows that can differentiate peptidoforms with different PTM distributions represent a powerful strategy to alleviate these challenges. Recently, a new Parallel Accumulation with Mobility Aligned Fragmentation (PAMAF™) operating mode for high-resolution ion mobility-mass spectrometry (HRIM-MS) analysis based on the structures for lossless ion manipulation (SLIM) technology was introduced. Here, we first assessed the performance of PAMAF mode for protein succinylation analysis using synthetic succinylated peptides, demonstrating residue-level differentiation of co-eluting isomers and isobars and precise PTM site localization. We leveraged this novel approach to investigate succinylome remodeling in kidney tissues from wild-type and Sirtuin-5 (Sirt5) knock-out mice, a NAD+-dependent lysine de-succinylase. PAMAF acquisitions yielded ~1000 confidently identified and accurately quantified succinylated peptides and sites from mouse kidney. Sirt5 regulated succinylation of mitochondrial proteins involved in metabolic processes, including fatty acid oxidation, the tricarboxylic acid cycle, and propionate metabolism. SIGNIFICANCE: Understanding the dynamic remodeling of the protein post-translational modification landscape is critical to gain insights into the underlying molecular mechanisms of biological systems. Lysine succinylation is a recently discovered reversible post-translational modification (PTM), that regulates various biological processes and associates with diverse diseases. However, this PTM is poorly characterized, partly due to analytical barriers. Here, we present a novel mass spectrometry (MS) methodology leveraging high-resolution ion mobility (HRIM) spectrometry and Parallel Accumulation with Mobility Aided Fragmentation (PAMAF) technology to profile and quantify succinylated peptides. The unique combination of liquid chromatography, ion mobility in a very long ion path (13 m), and alternate acquisition of MS and MS/MS spectra for all ions entering the mass spectrometer provided comprehensive profiling and accurate quantification of succinylated peptides in complex matrices. This technology enabled confident resolution of succinylated isomeric peptides, that could not be differentiated without high-resolution ion mobility separation and subsequent MS/MS PTM site identification. We investigated the kidney succinylome of Sirtuin-5 (desuccinylase) knockout mice compared to wild-type mice, with over 1000 succinylated peptides identified and quantified. We analyzed the hypersuccinylation of proteins upon Sirtuin-5 deletion, especially of mitochondrial proteins involved in diverse metabolic processes.

Keywords:  High-resolution ion mobility-mass spectrometry; PTM site localization; Parallel accumulation with mobility aligned fragmentation; Post-translational modifications; Sirtuin 5; Succinylation

DOI:  https://doi.org/10.1016/j.jprot.2026.105625
Acta Parasitol. 2026 Feb 09. 71(1): 30

Effects of Toxoplasma Gondii Type II Infection on Serum Serotonin Concentration and Indoleamine 2,3-Dioxygenase Gene Expression in Balb/c Mice.

Elham Kordserkeche, Jasem Saki, Reza Arjmand, Mohammad Amin Behmanesh, Saeedeh Shojaee.

   BACKGROUND: T. gondiiis an obligate intracellular protozoan that infects approximately one-third of the global population. Research has increasingly suggested a connection between toxoplasmosis and alterations in behavior. This study aims to investigate the effects of T. gondii infection on serum serotonin levels and the expression of the indoleamine 2, 3-dioxygenase (IDO) gene in the brain cells of Balb/c mice.
METHODS: A total of 84 female Balb/c mice were utilized in this study, with 42 assigned to the experimental group and 42 to the control group. The mice were further divided into six subgroups, each containing seven mice. Serum serotonin levels were quantified using the ELISA method, while the expression of the IDO1 gene was assessed through quantitative real-time PCR.
RESULTS: It is observed that the serotonin serum concentration in the infected Balb/c mice was substantially higher than the non-infected groups on the day 10th (371.17 ± 53.391 vs. 233.50 ± 1.225, p < 0.0001), 20th (283.33 ± 41.707 vs. 233.33 ± 1.033, p < 0.05 ), 30th (269.17 ± 36.766 vs. 233.67 ± 0.516, p < 0.05) and 40th (291.50 ± 62.956 vs. 233.67 ± 1.033, p < 0.05) post-infection, while the serotonin serum was dramatically diminished in the infected groups rather than the control mice on day 60th (197.50 ± 23.998 vs. 233.17 ± 1.472, p < 0.01). Notably, the expression of the IDO1 gene in brain cells increased by 5.65-fold on day 10 post-infection, followed by downward trends by day 40th (1.91-fold) was observed. Moreover, sharp fluctuations also took place on the 50th and 60th .
CONCLUSION: It is conclusively revealed that the serum level of serotonin and IDO1 mRNA expression were significantly higher in T.gondii infected Balb/c mice than normal control group. However, future investigations could explore therapeutic interventions targeting IDO1 or serotonin pathways to mitigate neurological impacts in chronic T.gondii infections.

Keywords:   Toxoplasma gondii ; 3-dioxygenase; Brain; Indoleamine 2; Serotonin; Serum

DOI:  https://doi.org/10.1007/s11686-025-01213-w
bioRxiv. 2026 Jan 31. pii: 2026.01.31.703051. [Epub ahead of print]

F26BP enables control of glycolysis rate independent of energy state.

Megan M Kober, Xinyi Yang, Bradley A Webb, Denis V Titov.

Glycolysis is a conserved metabolic pathway that produces ATP and biosynthetic precursors. Multiple allosteric regulators control glycolytic enzymes in vitro . For example, phosphofructokinase (PFK) is allosterically regulated by fructose-2,6-bisphosphate (F26BP), ATP, ADP, AMP, citrate, acyl-CoA, and inorganic phosphate. It is not well understood which properties of homeostasis are enabled by each of these regulators, and whether they perform redundant or distinct functions. Using mathematical modeling and experiments with human cells lacking F26BP, we demonstrate that F26BP alters glycolytic rate independent of cellular ATP demand-a unique function not shared by other regulators. We also identified several downstream glycolytic intermediates as novel regulators of F26BP levels. Our findings clarify the role of F26BP as a unique regulator that controls the glycolytic rate independently of the cellular energy state in response to hormone and biosynthetic precursor levels. The F26BP regulatory circuit enables respiratory fuel selection and biosynthesis from glycolytic intermediates.

DOI: https://doi.org/10.64898/2026.01.31.703051
bioRxiv. 2026 Feb 06. pii: 2026.02.03.703592. [Epub ahead of print]

PTMOverlay: A Proteomic Tool to Visualize Post-Translational Modifications Across Evolution.

Camille Krieger, Zachary Everton, Youngki You, Brandon Lewis, Thomas Bank, Meagan C Burnet, Sarai Williams, Hanna E Walukiewicz, Christopher V Rao, Alan J Wolfe, Samuel H Payne, Ernesto S Nakayasu.

Evolutionary conservation has been considered a hallmark of essential basic functions in cells. Therefore, the study of evolutionarily conserved post-translational modifications (PTMs) can provide insight into their role in protein function. In this context, mass spectrometry can identify and quantify thousands of PTM sites. However, a major bottleneck lies in analyzing the large amounts of data collected by the mass spectrometer. Here we address the need for a protein sequence alignment tool for multiple PTMs across several species. We developed a tool named PTMOverlay that takes peptide identification output files and overlays PTM sites onto multiple protein sequence alignments. Examining 31 bacteria isolates, we combined their protein sequences with select PTM types, including acetylation, phosphorylation, monomethylation, dimethylation, and trimethylation. The tool revealed a variety of conserved modification sites on the bacterial central carbon metabolism. Further structural analysis revealed possible interactions between methylated arginine and lysine residues with phosphothreonine/serine sites on the homodimer interface of enolase. Overall, this tool can parse large amounts of mass spectrometry data and allows for more informed and efficient selection of sites for future studies of protein function.

DOI: https://doi.org/10.64898/2026.02.03.703592
IMA Fungus. 2026 ;17 e168980

Genome-wide identification and expression profiling of the histone deacetylase gene family in Fusarium oxysporum.

Hong-Xin Liao, Jin-Rui Wen, Hong-Mei Shi, Huan-Qi Cun, Yun-Ju Hong, Zhang-Feng Hu, Fu-Rong Xu, Sulukkana Noiprasert, Kanyaphat Apiwongsrichai, Xiao-Yun Liu, Xian Dong.

  Histone deacetylases (HDACs) are key epigenetic regulators governing chromatin structure and gene expression, playing critical roles in growth, development, virulence, and multi-stress resistance of plant-pathogenic fungi. Despite their importance, the HDAC gene family (FoHDACs) in Fusarium oxysporum remains poorly characterized. Through genome-wide analysis, we identified 11 FoHDAC genes, phylogenetically classified into three subfamilies: Class I (2 genes), Class II (2 genes), and SIR2 (7 genes). Subcellular localization predicted 6 in the nucleus, 3 in the cytoplasm, and 2 in mitochondria, indicating functional diversity across organelles. Structural analyses revealed conserved domains/motifs specific to each subfamily. Genes showed asymmetric distribution across 6 chromosomes with no recent duplication events. Promoter analysis identified 22 putative cis-elements, including antioxidant (ARE, as-1) and stress response elements (STRE), linking FoHDACs to development and environmental responses. Functional annotation highlighted putative roles in transcriptional regulation, macromolecular catabolism, and heterochromatin assembly beyond core HDAC activity. Molecular docking showed binding affinities < -5 kcal/mol with significant differences across subfamilies. RT-qPCR revealed stage-specific expression: 8 genes peaked in dormant conidia, were suppressed during germination, and recovered during growth/sporulation; 2 showed continuous activation, and 1 was sporulation-specific. Abiotic stresses induced stimulus-dependent regulation, e.g., 33.67-fold repression of FoHST3 under salt stress and > 100-fold induction of FoHOS3 under cold stress. Collectively, our findings reveal that FoHDACs exhibit substantial functional diversity, forming a sophisticated regulatory network mediating fungal development and environmental adaptation.

Keywords:  Environmental stress response; Fusarium oxysporum; epigenetic regulation; genome-wide identification; histone deacetylase

DOI:  https://doi.org/10.3897/imafungus.17.168980
PLoS Pathog. 2026 Feb;22(2): e1013920

Mitochondrial ribosomes in apicomplexan and trypanosomatid parasites: Dissimilar drivers of complexity and convergent features.

Ondřej Gahura, Prashant Chauhan.

DOI: https://doi.org/10.1371/journal.ppat.1013920
Front Immunol. 2025 ;16 1691005

Adrenergic signaling during parasitic infections.

Patrycja Gardias, Piotr Bąska.

  Adrenergic signaling plays a critical role in modulating immune and physiological responses during parasitic infections. Catecholamines such as adrenaline and noradrenaline interact with adrenergic receptors (ARs) to regulate immune cell activity, inflammation, and systemic processes. This review highlights the involvement of adrenergic pathways in infections caused by protozoa (Trypanosoma spp., Plasmodium spp., Toxoplasma gondii, Leishmania spp.) and helminths (cestodes, nematodes, and flukes). Central nervous system invasion by parasites is associated with neurodegeneration, mediated by immune and adrenergic mechanisms. Dysregulation of adrenergic signaling can exacerbate infection outcomes or contribute to immune-mediated tissue damage. Understanding these mechanisms provides insights into the potential of targeting adrenergic pathways to improve therapeutic strategies and manage parasitic infections effectively.

Keywords:  adrenaline; adrenoreceptors (ARs); central nervous system; helminths; neuroinflammation; noradrenaline; parasites; protozoa

DOI:  https://doi.org/10.3389/fimmu.2025.1691005
Cells. 2026 Jan 26. pii: 230. [Epub ahead of print]15(3):

The Glutamine-α-Ketoglutarate Metabolic Axis Controls Vascular Smooth Muscle Cell Function.

Kelly J Peyton, Xiao-Ming Liu, Giovanna L Durante, William Durante.

  Glutamine is a known regulator of vascular smooth muscle cell (VSMC) function, but the molecular pathways underlying this response remain incompletely understood. This study investigated how glutamine metabolism influences VSMC behavior and identified the responsible enzymes and metabolites. Glutamine deprivation markedly reduced VSMC proliferation, migration, and collagen synthesis, while modestly decreasing viability. Pharmacological inhibition of glutaminase-1 (GLS1) or aminotransferases (AT) similarly suppressed these cellular functions, whereas inhibiting glutamate dehydrogenase 1 (GLUD1) had no effect. Metabolite analysis revealed that glutamine deprivation or AT inhibition, but not GLUD1 inhibition, reduced intracellular α-ketoglutarate (αKG) concentrations, establishing AT as the primary enzyme converting glutamine-derived glutamate to αKG. To identify which metabolite drives VSMC responses, glutamine-starved cells were supplemented with various glutamine-derived molecules. The cell-permeable αKG analog dimethyl-αKG significantly restored VSMC proliferation, migration, collagen synthesis, and survival, while ammonia only enhanced viability, demonstrating αKG's primary role in mediating glutamine-dependent functions. These findings establish that glutamine metabolism via the GLS1-AT-αKG pathway is a critical driver of VSMC activation and survival. Targeting this glutamine-αKG metabolic axis through GLS1 inhibition, AT blockade, or downstream αKG disruption offers a compelling therapeutic strategy for ameliorating fibroproliferative vascular diseases, including atherosclerosis, post-angioplasty restenosis, and pulmonary hypertension.

Keywords:  aminotransferase; collagen; glutaminase; glutamine; migration; proliferation; vascular smooth muscle cells; viability; α-ketoglutarate

DOI:  https://doi.org/10.3390/cells15030230
Mol Cell Biochem. 2026 Feb 14.

The role and mechanism of histone deacetylase in COPD.

Huifang Tang, Qian Gao, Shu Xie.



Keywords:  Airway remodeling; Chronic obstructive pulmonary disease; Emphysema; Histone deacetylases; Inflammation; Skeletal muscle dysfunction

DOI:  https://doi.org/10.1007/s11010-026-05503-3
Proc Natl Acad Sci U S A. 2026 Feb 17. 123(7): e2529141123

Mining lysine post-translational modification sites by integrating protein language model representations with structural context.

Mengqi Luo, Xiaohong Zhu, Chen Bai, Arieh Warshel, Luonan Chen.

  Lysine (Lys/K) residues serve as major hubs for post-translational modifications (PTMs) owing to the chemical versatility of their ε-amino groups, giving rise to diverse regulatory functions. Accurate and efficient identification of modified lysine residues therefore requires computational models that can effectively capture both sequence and structural information while minimizing domain-specific feature engineering. In this study, we propose a unified deep learning framework for lysine PTM site identification that integrates sequence representations derived from a protein language model with atom-level three-dimensional structural features. This framework can be consistently applied to multiple lysine PTM types using a shared modeling strategy. As an application, we used the model to predict potential PTM site on human C-type lectin domain family 12 member A (hCLEC12A) and evaluated their functional relevance through all-atom molecular dynamics simulations. The simulations indicate that the predicted lysine residues influence the stability and binding behavior of the hCLEC12A-antibody 50C1 complex. Overall, this work presents an integrative computational framework for lysine PTM site mining and functional analysis.

Keywords:  deep learning; lysine PTM site mining; molecular dynamics (MD) simulations; protein language model; structural information

DOI:  https://doi.org/10.1073/pnas.2529141123
Nucleic Acids Res. 2026 Feb 05. pii: gkag101. [Epub ahead of print]54(4):

Scaffolding of the H4K5ac chromatin remodeling complex by lncRNA MAHAC mediates epithelial-mesenchymal transition.

Kai-Wen Hsu, Jeng-Shou Chang, Joseph Chieh-Yu Lai, Li-Hao Yang, Pei-Hua Peng, Tzu-Chin Lin, Kou-Juey Wu.

Anchoring of a chromatin remodeler complex by long non-coding RNAs (lncRNAs) is a frequently utilized mechanism for lncRNAs to regulate gene expression. Hypoxia is a microenvironmental condition that plays a crucial role in promoting tumor progression. We previously identified a hypoxia-inducible lncRNA, RP11-390F4.3, that regulates epithelial-mesenchymal transition (EMT) without a delineated mechanism. Here, we show that the lncRNA RP11-390F4.3 (renamed MAHAC: MAintenance of Histone ACetylation) specifically induces histone H4 lysine 5 acetylation (H4K5ac) mark and promotes the deposition of H4K5ac mark on the promoters of EMT transcription factors. MAHAC scaffolds the ILF3/NF90-ILF2-CBP complex, which is co-localized with the members of the complex inside the nucleus under hypoxia. The minimal MAHAC region (nt 686-741) required for scaffolding the complex was mapped, and it induces allosteric activation of H4K5ac in in vitro histone acetyltransferase assay. This minimal MAHAC region is essential for hypoxia-induced EMT, migration, invasion, and H4K5ac activation. These findings demonstrate that hypoxia-induced MAHAC represents an unexplored allosteric regulator of H4K5ac that activates EMT and induces tumor progression.

DOI: https://doi.org/10.1093/nar/gkag101
Commun Biol. 2026 Feb 09. 9(1): 178

Lysine malonylation regulates human sperm motility.

Yimin Cheng, Yan Tian, Houyang Chen, Shenglin Peng, Ying Chen, Zhen Peng, Tao Luo.

Lysine malonylation (Kmal) is a novel post-translational modification (PTM) implicated in numerous biological processes. Our recent study finds that human sperm proteins are modified by Kmal, but the functional significance of Kmal in human sperm remains unclear. The present study shows that Kmal primarily occurs in human sperm tail proteins with molecular weights ranging from 15 to 250 kDa. Similar to somatic cells, Kmal is derived from malonyl-CoA, with acyltransferase P300 and sirtuin 5 (SIRT5) potentially acting as the writer and eraser, respectively, for Kmal in human sperm. The Kmal level in asthenozoospermic sperm is significantly higher than that in normozoospermic sperm and exhibits a negative correlation with progressive motility. Elevated Kmal levels in asthenozoospermic sperm are associated with reduced sperm SIRT5 and ATP levels, as well as inhibited glycolysis. Furthermore, the induction of sperm Kmal by sodium malonate significantly diminishes the motility and penetration ability of normozoospermic samples by reducing sperm [Ca2+]i, ATP, and cAMP levels, and by suppressing glycolysis and PKA activity. Our findings elucidate the regulatory function of Kmal in human sperm motility and its association with asthenozoospermia, thereby offering insights for the diagnosis and treatment of idiopathic male infertility.

DOI: https://doi.org/10.1038/s42003-026-09683-y
Zhonghua Xin Xue Guan Bing Za Zhi. 2026 Feb 24. 54(2): 224-228

[Regulatory effects and mechanisms of protein post-translational modifications on BK channel in metabolic syndrome-related diseases].

S Y Fan, Z Y Zhang, R X Wang.

DOI: https://doi.org/10.3760/cma.j.cn112148-20260105-00012
Cancer Res. 2026 Feb 09.

Subcellular Redistribution of Endomembrane GPR15 Promotes NAD+-Mediated Metabolic Reprogramming and Boosts 5-FU Chemosensitivity in Colorectal Cancer.

Zhiying Yue, Wentao Dai, Zhuoran Cao, Bin Hu, Ziyuan Wang, Xinrun Ma, Da Qin, Taiyu Zhang, Qingqing Sang, Jing Mei, Tianci Yu, Yong Zhou, Zai Luo, Junming Xu, Zengjin Yuan, Yuan-Yuan Li, Jinyan Zhang, Chen Huang, Zhengfeng Yang.

G protein-coupled receptors (GPCRs) are increasingly recognized for their organelle-specific functions in cancer. A better understanding of the mechanisms governing their dynamic subcellular distribution and functional coordination is essential for developing spatially targeted therapies that exploit the subcellular signaling networks of GPCRs. Here, we found that Golgi-localized GPR15 underwent spatiotemporal trafficking to enhance 5-fluorouracil (5-FU) chemosensitivity in colorectal cancer. Dependent on Gαq, GPR15 associated with and restrained PARP4 enzymatic activity in the Golgi apparatus to drive cytosolic NAD⁺ accumulation. MGST1 interacted with and navigated GPR15 redistribution to mitochondria to increase mitochondrial NAD+ abundance, which fueled central carbon metabolism and activated downstream metabolic networks to prime tumors for 5-FU cytotoxicity. Treatment with the PARP inhibitor rucaparib showed potent synergy with 5-FU and demonstrated robust tumor suppression in patient-derived organoids and xenograft models through NAD⁺-mediated metabolic perturbation. This work establishes spatially encoded GPCR signaling as a druggable axis to potentiate chemotherapy efficacy, redefining intracellular receptor trafficking as an important regulator of metabolic plasticity in cancer therapy.

DOI: https://doi.org/10.1158/0008-5472.CAN-25-2586
Mol Biol Rep. 2026 Feb 13. 53(1): 383

Lipid droplets and major metabolic disorders.

William J Dechert, Guanglong He.

  Lipid droplets (LDs) are ubiquitous subcellular organelles playing crucial roles in lipid and energy homeostasis. They are constantly generated in the intramembrane space of the endoplasmic reticulum (ER) through unique mechanisms. Upon maturation, they bud off from the ER outer membrane into the cytosol, travel through the cytosolic microtubular network, and make contacts to most of the other subcellular organelles to perform their cellular functions. On the one hand, these organelles can grow or fuse with other smaller ones and serve as storage for extra cellular lipid products. On the other hand, when metabolic needs arise such as in nutrient deprivation or during exercises, the esterified lipids inside the LDs undergo stepwise lipolysis, e.g. basal and stimulated lipolysis, under the regulation of a set of proteins and kinases that are specifically targeted to the monolayer phospholipid membrane of the LDs. The dynamic homeostasis of their biogenesis and lipolysis is also intimately related to other cellular signaling pathways in a paracrine or endocrine manner which actively participate in the regulation of cellular homeostasis and systemic health. This review will summarize the current understanding of the underlying mechanisms mediating the biogenesis and metabolic impact of LDs in normal and disease status with a focus on their roles in propelling and sustaining chronic inflammation.

Keywords:  Chronic inflammation; Lipid droplets (LDs); Lipolysis; Lipophagy; Metabolism

DOI:  https://doi.org/10.1007/s11033-026-11563-x
Chem Biodivers. 2026 Feb;23(2): e03194

Isocitrate Dehydrogenase Inhibitors in Acute Myeloid Leukemia.

Qiuzi Dai, Zi Yang, Binsheng He, Yaqian Li.

  Mutations in isocitrate dehydrogenase genes (IDH1 and IDH2) are common in acute myeloid leukemia (AML), occurring in up to 30% of AML cases. Mutations in IDH lead to abnormal epigenetic regulation in AML cells and block differentiation. Inhibitors of mutated IDH1 and IDH2, vorasidenib, ivosidenib, olutasidenib, and enasidenib, respectively, were recently approved by the FDA for relapsed/refractory AML. In this review, we mainly focus on IDH inhibitors in leukemia therapy, including the discovery, structure optimization, activity of IDH inhibitors, and applications, which provided the reference for the discovery of new anticancer agents.

Keywords:  acute myeloid leukemia; anticancer; isocitrate dehydrogenase 1 (IDH1); isocitrate dehydrogenase 2 (IDH2)

DOI:  https://doi.org/10.1002/cbdv.202503194