Micronutrients shape FOXP2 activity: Mechanistic insights from retinoic acid, folic acid and pyrroloquinoline quinone.

Human Umbilical Cord-derived Mesenchymal Stromal Cells (hUC-MSCs) represent a promising candidate for regenerative medicine, though their therapeutic potential is constrained by replicative senescence. Pyrroloquinoline quinone (PQQ), a redox-active coenzyme, has been reported to protect against cellular aging. However, its precise role and mechanism of action in mitigating replicative senescence of hUC-MSCs remain to be elucidated. This study employed an integrated approach of phenotypic screening and transcriptomic profiling to systematically evaluate the anti-senescence effects of PQQ on replicatively senescent hUC-MSCs. Our results indicated that PQQ treatment enhanced proliferative capacity, reduced senescence-associated β-galactosidase (SA-β-gal) activity, and attenuated G1 phase cell cycle arrest. Moreover, PQQ improved mitochondrial membrane potential, reduced intracellular reactive oxygen species (ROS) accumulation, and attenuated telomere attrition. RNA sequencing analysis suggests that PQQ treatment appears to alleviate senescence-related transcriptional features, which is consistent with the observed phenotypic improvements. Gene Set Enrichment Analysis (GSEA) revealed a significant upregulation of pathways governing cell cycle progression and DNA replication following PQQ intervention. Key Driver Analysis (KDA) further identified regulators within these pathways, including PLK1, MCM5, and CDC6. Subsequent qPCR validation showed that the expression of these genes, which are critical for DNA replication initiation and mitotic progression, was downregulated in senescent cells and increased following PQQ treatment. In conclusion, the effect of PQQ on the replicative senescence of hUC-MSCs may be related to the upregulation of genes associated with the cell cycle and DNA replication.

Study on DepA preparation by cell free expression system and elucidation of DON biotransformation mechanisms by molecular docking.

Improvement of spermogenesis impairment induced by high-fat diet in obese mice through pyrroloquinoline quinone regulation of glycolysis pathway.

Pyrroloquinoline quinone (PQQ), an o-quinone-type nutrient, has been shown to exert diverse beneficial effects on the biochemical and physiological processes of mammals. However, the molecular mechanisms underlying these effects remain incompletely understood. Here, through screening of metabolite-sensing G protein-coupled receptors (GPCRs)─which respond to metabolites produced by gut microbiota or derived from nutrients─we found that PQQ selectively activates G-protein-coupled receptor 35 (GPR35) and characterized the molecular basis of its ligand recognition. Using a transforming growth factor α shedding assay, we demonstrated that PQQ selectively activated GPR35, a class A rhodopsin-like GPCR expressed in various tissues, including adipose tissue and the gastrointestinal tract. PQQ also promoted β-arrestin 1 recruitment to the plasma membrane, further supporting its role as a GPR35 agonist. Direct binding of PQQ to GPR35 was demonstrated using a clickable photoaffinity probe derived from PQQ. Molecular docking simulation and site-directed mutagenesis revealed that the 2-carboxylic acid moiety of PQQ forms critical hydrogen bonds with Arg100, Tyr101, and Arg151 of GPR35. Additionally, Phe163 appears to contribute to π-H interaction with PQQ. These findings indicate that PQQ functions as a food-derived agonist of GPR35 and provide new insights into the molecular mechanisms underlying the potential beneficial effects of PQQ.

No effect of pyrroloquinoline quinone on mouse body weight and energy metabolism with the concomitant increase in mitochondrial biogenesis and antioxidant ability

Brassinosteroids (BRs) play important roles in regulating nutrient uptake, and phosphorus (P) deficiency severely limits rice productivity. However, whether and how BRs mediate P use efficiency (PUE), particularly via root-rhizosphere processes, remains unclear. Over three years, we ran two pot experiments in a low-P soil (Olsen-P 6.8 mg kg⁻¹). Experiment 1 (Genotype × P): YG2 (strong low-P tolerant variety) and ZD88 (weak low-P tolerant variety) were grown under no P (0P) and normal P (NP) conditions. Experiment 2 (Chemical application× P): plant roots were irrigated with 2,4-epibrassinolide (2,4-EBL) or a BRs biosynthesis inhibitor under both 0P and NP rates, with distilled water as the control. Results showed that, relative to NP, 0P significantly decreased root BR (2,4-epibrassinolide and 2,8-homobrassinolide) content in both genotypes, with a smaller reduction in YG2 than in ZD88 under 0P. YG2 outperformed ZD88 in grain yield and PUE at both P rates, especially at 0P, mainly due to the enhancement of early-stage (before panicle initiation) P accumulation driven by its elevated BR content. Under 0P, YG2 also exhibited superior root morph-physiological traits, viz. root length, root activity, malate secretion, along with higher pyrroloquinoline quinone biosynthesis protein C (pqqC) gene copies and greater resin-P content in the rhizosphere. At 0P, applying 2,4-EBL increased root BR content, activated BR-signaling gene expression, improved root and rhizosphere traits, and enhanced early-stage P accumulation, whereas applying BRs biosynthesis inhibitor had opposite effects. Applying 2,4-EBL additionally favored recruitment of the phosphate-solubilizing bacterium Massilia. Correlation and structural equation model analyses supported a pathway whereby elevated BR content activated BR signaling and downstream cascades that strengthened root performance and enriched Massilia, thereby increasing absorptive capacity and rhizosphere P supply. Overall, BRs mediate grain yield and PUE by optimizing root-rhizosphere cooperation under P-deficiency conditions.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12284-025-00872-7.

The halotolerant endophytic bacterial Pseudomonas strain EB3 isolated from the roots of the mangrove plant species Avicennia alba, has been reported to promote plant growth and mitigate the adverse effects of salt stress. However, the genetic mechanisms of the strain that may explain these processes are unknown. This study aimed to determine the whole genome sequence of EB3 and conduct expression analysis of EB3 genes putatively involved in salt tolerance and plant growth promotion. EB3-inoculated banana (Musa acuminata cv. Berangan) plantlets were subjected to 100mM sea salt. These inoculated plants exhibited significantly improved growth compared to non-inoculated controls under the same salinity stress. Whole-genome sequencing of EB3 revealed a genome size of 6 006 826bp. Phylogenetic analysis based on whole-genome comparison indicated that EB3 is closely related to Pseudomonas juntendi. Functional annotation of the genome identified a large number of genes associated with key biological processes, including stress resistance, iron uptake system, plant root colonization, and plant growth promotion. The increased expression of succinate-semialdehyde dehydrogenase (gabD), pyrroloquinoline quinone biosynthesis proteins (pqqBDEF), acetylglutamate kinase (argB), NADP-specific glutamate dehydrogenase (gdhA), N-acetylglutaminylglutamine synthetase (ngg), and superoxide dismutase family protein (sodC) genes in EB3, when EB3-inoculated plants were placed under salt stress, further supported their potential involvement in salt tolerance and growth-promoting activities. Together, the genomic insights and gene expression data confirm the functional potential of the EB3 strain as a plant growth-promoting bacterium (PGPB) even under saline conditions.

Mitochondrial biogenesis (MB) is involved in the regulation of cellular energy metabolism, stress response, and survival. This review examines therapeutic approaches to acute kidney injury (AKI) that target MB, emphasizing clinical research findings and translational strategies in this field. AKI is a severe condition with high mortality and often leads to chronic kidney disease. AKI suppresses MB, resulting in mitochondrial dysfunction, oxidative stress, and further renal damage. Furthermore, studies have shown that ischemia-reperfusion-, sepsis-, and drug-induced AKI inhibit MB and subsequent kidney injury. Studies have shown that targeting MB through genetic and pharmacological interventions can alleviate AKI by restoring mitochondrial function and improving renal outcomes. Small molecule compounds, such as pyrroloquinoline quinone, ZLN005, and resveratrol, can enhance MB, offering potential therapeutic benefits. Nonetheless, further studies are needed to ensure efficacy across different models and mitigate related side effects. Future research should focus on optimizing drug design, understanding MB regulation, and conducting clinical trials to establish effective treatments for AKI.

Carbon-phosphorus coupling in reddish paddy fields under long-term organic material input: Temporal dynamics and the role of pqqC-harboring bacteria as a driver.

Testicular torsion–detorsion (T/D) induces ischemia–reperfusion injury, leading to mitochondrial dysfunction, oxidative stress, apoptosis, and spermatogenic impairment. Pyrroloquinoline quinone (PQQ), a redox cofactor with mitochondrial-protective, antioxidant, and anti-apoptotic properties, was evaluated for its therapeutic potential in a rat T/D model. Young adult male Sprague-Dawley rats underwent 720° spermatic cord rotation for 2 h followed by detorsion and were assigned to T/D or T/D + PQQ groups, with sham-operated controls run in parallel. PQQ (400 mg/kg body weight) was administered orally once daily for 4 weeks. T/D resulted in severe disruption of testicular architecture, disorganization of seminiferous epithelium, reduced sperm count and testis-to-body weight ratio, increased hypoxia-inducible factor-1α and malondialdehyde, decreased superoxide dismutase 2, impaired oxidative phosphorylation (OXPHOS), and enhanced apoptosis. Notably, PQQ treatment significantly preserved testicular structure, improved sperm counts, reduced oxidative stress, restored OXPHOS, and suppressed apoptosis (all p < 0.05. T/D + PQQ vs. T/D). These findings indicate that PQQ protects against T/D-induced testicular injury. The underlying mechanisms may involve the attenuation of oxidative stress, the preservation of mitochondrial function, and the limitation of apoptosis, supporting its potential as a therapeutic strategy for testicular IRI.

Multiple-mode immunoassays have the advantages of self-correction, self-validation, and high accuracy and reliability. In this work, we developed a strategy for the design of triple-mode immunoassays with the self-assemblies of three-in-one small molecules as signal reporters. Pyrroloquinoline quinone (PQQ), with a well-defined redox peak and excellent spectroscopic and fluorescent signals, was chosen as the signaling molecule. PQQ was coordinated with Cu2+ to form metal–organic nanoparticle as the signal label. Hexahistidine (His6)-tagged recognition element (recombinant streptavidin) was attached to the Cu-PQQ surface through metal coordination interaction between the His6 tag and the unsaturated metal site. The captured Cu-PQQ nanoparticle released a large number of PQQ molecules under an acidic condition, which could be simultaneously monitoring by electrochemical, UV-vis, and fluorescent techniques, thereby allowing for the development of triple-model immunoassays. The three methods were used to determine the concentration of carcinoembryonic antigen (CEA) with the detection limits of 0.01, 0.1, and 0.1 ng/mL, respectively. This strategy opens up a universal route for the preparation of multiple-model signal labels and the oriented immobilization of bioreceptors for molecular recognition.

Pyrroloquinoline quinone targets senescent osteoclasts and reduces spinal pain and endplate degeneration in a lumbar spine instability mouse model

Gestational diabetes mellitus (GDM) is a prevalent metabolic disturbance in pregnancy. This study analyzed the mechanism of maternal GDM inducing myocardial injury in male offspring through growth differentiation factor-15 (GDF-15). Pregnant rats were randomly assigned to the GDM-mother (streptozotocin [STZ] induction) and the Control-mother (normal saline injection) groups. Here, 32 male offspring from the Control-mother group and 92 from the GDM-mother group were used for experiments. The myocardial ischemia model was established by left anterior descending (LAD) coronary artery ligation in 6-week-old male offspring. Male offspring in the GDM-mother group were treated with sh-Gdf15, pyrroloquinoline quinone, or rotenone. Cardiac function, oxidative stress-associated indicators, myocardial infarct size and necrosis, inflammatory infiltration, cardiomyocyte apoptosis, mitochondrial damage, and Gdf15 mRNA and protein expression were examined using echocardiography, kits, TTC/H&E/TUNEL staining, flow cytometry, RT-qPCR, and western blot. GDM maternal rats had elevated blood glucose and a reduced body weight, representing successful modeling. Prenatal STZ exposure did not affect blood glucose but decreased the body weight in male offspring. The baseline cardiac function was not affected by prenatal STZ exposure, whereas LAD ligation-induced ischemia caused severe cardiac dysfunction in GDM male offspring versus controls. GDF-15 was upregulated in GDM rat male offspring, and its knockdown alleviated myocardial injury. Adult male offspring of GDM rats exhibited pronounced mitochondrial damage, and mitochondrial homeostasis restoration improved ischemia-caused cardiac dysfunction. Suppressing mitochondrial function partly abrogated cardioprotective effects of Gdf15 knockdown. Maternal GDM promoted myocardial injury in male offspring by upregulating GDF-15 to aggravate mitochondrial damage.

Pyrroloquinoline quinone (PQQ)-binding proteins are found in diverse species and play key roles in the central metabolism of many methylotrophic bacteria, acting as redox-active cofactors in their alcohol dehydrogenase (ADH) enzymes. These enzymes also require a Lewis acidic metal ion to activate PQQ, and the 2011 discovery of lanthanide (Ln3+)-dependent ADH enzymes sparked a surge of interest in understanding their functional properties. However, key questions remain regarding the mechanism, metal ion-dependence, and electron transport processes of these enzymes. We report mechanistic, structural, and computational studies on an artificial metalloenzyme (ArM) containing a biomimetic active site that binds Ln3+, PQQ, and catalyzes benzyl alcohol dehydrogenation. These studies provide insights into the potential structure-function relationships present in natural MDHs. Examining the relative reactivities of substituted benzyl alcohol substrates revealed a kinetic isotope effect of 2.9 ± 0.4 and a linear free energy relationship consistent with one of the two mechanistic pathways widely proposed to operate in ADHs. Preparing ArMs with metal ions spanning the rare earth series, we observed decreasing reactivity with increasing Lewis acidity, a pattern consistent with that of natural ADH assays. In contrast to patterns observed in natural ADH assays, addition of ammonia had no effect on catalysis. Finally, investigating the role of a conserved active site residue through X-ray diffraction and molecular dynamics simulations, revealed a PQQ/substrate access channel critically regulated by this site. Together, these studies bear new insights into the mechanism, metal ion-dependence, and conformational dynamics associated with PQQ and rare earth-dependent enzymes.

The low oxidation activity of pyrroloquinoline quinone (PQQ)-dependent dehydrogenase (DepA) toward deoxynivalenol (DON) restricts its practical application in the food industry. Here, bioinformatics analysis indicated that the N-terminal loop of DepA acts as a lid that swings above the active pocket and plays an important role in controlling substrate entry. Considering that different PQQ-dependent dehydrogenases have different N-terminal loop lengths, we constructed DepA N-terminal truncation mutants. The catalytic efficiency (kcat/Km) of the best truncation mutant, N21, increased by 7.9-fold. Computational analysis suggested that mutant N21 maintains the open conformation of the N-terminal loop and widens the substrate channel to increase the level of substrate entry. In addition, the active pocket of mutant N21 was reshaped, which strengthened the interaction between DON and the active cavity residues and reduced the proton transfer distance, enhancing catalytic activity. This study provides new insights into engineering the catalytic activity of PQQ-dependent dehydrogenases.

Coproduction of single cell protein and pyrroloquinoline quinone by Hyphomicrobium denitrificans using molasses and biogas slurry.

PYR/PYL (pyrroloquinoline quinone resistance/PYR1-like) are receptors for abscisic acid (ABA) in plants and play a crucial role in responses to abiotic stress. In this study, we identified 63 members of the StPYL gene family at the tetraploid whole-genome level in potatoes. We analyzed the physicochemical properties of these 63 StPYLs and constructed a phylogenetic tree using Arabidopsis thaliana and potato (Solanum tuberosum L.) cultivar ‘DM’ as the reference. By examining gene structure, conserved protein motifs, and collinearity, we found that StPYLs are highly conserved throughout evolution. The gene expression heat map under salt stress revealed that 57 StPYL genes are involved in the salt stress response. Among them, the expression level of StPYL9a-like changed significantly under salt stress. Through genetic transformation, we observed that overexpression of StPYL9a-like enhanced the growth and survival of potato plants under salt stress compared to the wild type. The contents of proline (Pro), superoxide dismutase (SOD), and chlorophyll in the leaves of overexpressing plants increased, while malondialdehyde (MDA) levels decreased. This suggests that StPYL9a-like positively regulates salt tolerance by affecting antioxidant enzyme activity and osmotic adjustment substances in potatoes. Subcellular localization demonstrated that StPYL9a-like is localized in the nucleus. This study provides a reference for the functional research of PYLs in potatoes, offers a basis for screening potato genes related to salt stress, and lays a foundation for developing salt-tolerant potato varieties.

Lanthanide(III)-dependent hydration of the methanol dehydrogenase cofactor, pyrroloquinoline quinone.

Pyrroloquinoline quinone grafted carboxymethyl chitosan with oxidized xanthan gum hydrogel for biomedical applications