IUBMB Life最新文献

{"title":"Black Sheep: Pseudokinases Bucking the Trend to Reveal Non-Catalytic Kinase Functions","authors":"James M. Murphy,&nbsp;Natalia Jura,&nbsp;Peter D. Mace","doi":"10.1002/iub.70125","DOIUrl":"10.1002/iub.70125","url":null,"abstract":"<p>Pseudokinases are the catalytically-dead counterparts of protein kinases and, over the past 20 years, have increasingly garnered attention as crucial signaling entities—comprehensively dispelling the possibility that they are merely evolutionary remnants or cellular passengers. The field has been framed by a sequence-based definition of a pseudokinase, where the absence of one or more of the three critical catalytic residues required for phosphoryl transfer in conventional protein kinases has allowed their classification. As a result, pseudokinases have been defined by their dissimilarity to active kinases, meaning they are the outcasts or black sheep of the kinome. Pseudokinases are prevalent in nature, accounting for 10% or more of the kinase complement throughout phyla, and have been reported to mediate diverse functions in controlling the activities of other enzymes allosterically, mediating signaling complex assembly, serving as conformational switches and as negative regulators of signaling flux. Here, we review our current understanding of the varied pseudokinase functions as a window toward understanding non-catalytic functions of conventional protein kinases, the challenges associated with defining pseudokinases—especially in cases where cryptic catalytic activities have been reported—and the emergence of pseudokinases as pharmacological targets.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Ancestral Mechanism of Calmodulin Binding to Cds1 Kinase Inhibits Catalytic Activity","authors":"Stephanie A. Manovella,&nbsp;Tingting Wang,&nbsp;Samuel N. Young,&nbsp;Toby A. Dite,&nbsp;Vineet Vaibhav,&nbsp;Steve Binos,&nbsp;Laura F. Dagley,&nbsp;Anh T. N. Nguyen,&nbsp;Anthony R. Means,&nbsp;Janni Petersen,&nbsp;John W. Scott,&nbsp;James M. Murphy,&nbsp;Christopher R. Horne","doi":"10.1002/iub.70128","DOIUrl":"10.1002/iub.70128","url":null,"abstract":"<p>Calmodulin is a highly conserved, calcium (Ca²⁺) sensor protein that is ubiquitous among eukaryotes. Ca²⁺ binding to Calmodulin induces a conformational change that facilitates interaction with, and activation of, serine/threonine protein kinases, including members of the CaMK family. Recently, Ca²⁺-Calmodulin binding to one such protein kinase, Checkpoint kinase 2 (CHK2), which is responsible for the regulation of cell cycle progression following DNA damage in mammalian cells, was shown to suppress CHK2 catalytic activity. Here, by applying biochemical, structural mass spectrometry and yeast genetic methods, we identify an analogous mode of inhibition of the fission yeast <i>Schizosaccharomyces pombe</i> CHK2 functional orthologue, Cds1, through direct binding of Ca²⁺-Calmodulin to the Cds1 kinase domain. Our studies assert an ancestral function for Calmodulin in suppressing the catalytic activity of CHK2 orthologs and highlight a mechanism by which Ca²⁺ flux can attenuate Cds1 catalytic activity to facilitate exit from the replication checkpoint and promote cell cycle progression.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148828803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise as a Programmable Regulator of Mitophagy Sensitivity in Aging Muscle and Age-Related Disease","authors":"Peng Ran,&nbsp;Lifang Yang","doi":"10.1002/iub.70127","DOIUrl":"https://doi.org/10.1002/iub.70127","url":null,"abstract":"<div>\u0000 \u0000 <p>Aging is increasingly recognized as a systems-level process marked by progressive deterioration of mitochondrial performance in tissues with high energetic demand, placing skeletal muscle at the center of systemic metabolic and functional decline. Beyond its mechanical role, skeletal muscle acts as a regulatory hub for energy homeostasis, redox balance, and inter-organ signaling, functions that depend critically on effective mitochondrial quality control. Emerging evidence indicates that age-related mitochondrial dysfunction arises not only from impaired biogenesis but also from dysregulated mitophagy, the selective autophagic removal of damaged mitochondria. Mitophagy is now understood as a dynamic, context-sensitive process integrating metabolic state, mechanical loading, and cellular stress, rather than a binary response to severe mitochondrial damage. Exercise represents a uniquely potent, non-pharmacological modulator of this process. By transiently perturbing cellular energy balance, calcium flux, and redox signaling, physical activity activates coordinated mitophagic and biogenic programs that promote mitochondrial renewal without precipitating energetic collapse. In contrast to chronic pathological stressors, exercise induces pulsatile, recoverable mitochondrial challenges that recalibrate quality-control thresholds. Importantly, mitophagic responses to exercise are heterogeneous and nonlinear. Exercise modality, intensity, frequency, and temporal organization generate distinct mitochondrial signals, producing fiber-type–specific and age-dependent adaptations. In aging muscle, elevated activation thresholds, delayed clearance kinetics, and lysosomal constraints frequently blunt adaptive mitophagy, indicating remodeling rather than a simple suppression of quality-control logic. This review integrates molecular, physiological, and translational evidence to redefine exercise as a precision regulator of mitophagy in aging skeletal muscle. This review proposes that tailored exercise strategies targeting mitophagy may provide a scalable, non-pharmacological approach to preserve mitochondrial quality and functional resilience during aging.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 8","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA-ATB Orchestrates Tumor Growth and Immune Responses Through the Modulation of IGF2BP2 in Non-Small-Cell Lung Cancer","authors":"Shifang Sun,&nbsp;Hailin Chen,&nbsp;Shanshan Rong,&nbsp;Chenwei Li,&nbsp;Decai Zhu,&nbsp;Er Hong","doi":"10.1002/iub.70085","DOIUrl":"10.1002/iub.70085","url":null,"abstract":"<div>\u0000 \u0000 <p>Long non-coding RNAs (lncRNAs) are known to play a vital role in regulating tumorigenesis. Previous studies have shown that long non-coding RNA modulated by transforming growth factor-beta (lncRNA-ATB) is overexpressed in non-small-cell lung cancer (NSCLC); however, the underlying mechanism of lncRNA-ATB as an oncogenic regulator remains elusive. This study elucidates the effect of lncRNA-ATB on cell proliferation, migration, and invasion of NSCLC cell lines (A549 and H522) and triggers cellular immune responses. The tumor microenvironment was simulated in BALB/c mice, and the in vivo pro-tumor effect of lncRNA-ATB was discovered. This study further explores the molecular mechanisms of lncRNA-ATB-mediated effects. The interaction of lncRNA-ATB with insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) has been found, and IGF2BP2 can play a role in tumor immune cell infiltration and tumor cell proliferation by stabilizing lncRNA-ATB. In conclusion, lncRNA-ATB plays a complex regulatory role in the progression of NSCLC and may serve as a potential target for future treatment. This study provides valuable insights into the complex interactions of lncRNAs in the pathogenesis of NSCLC, and the robust methodology and comprehensive analysis presented in this study contribute to advancing our understanding of the molecular mechanisms underlying NSCLC progression.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Telomeric Role of RAP1 in Facilitating NF-κB Activation and Driving Hepatocellular Carcinoma Progression","authors":"Rui Liu,&nbsp;Nannan Fu,&nbsp;Shuang Li,&nbsp;Tao Liu","doi":"10.1002/iub.70123","DOIUrl":"10.1002/iub.70123","url":null,"abstract":"<div>\u0000 \u0000 <p>RAP1 (TERF2IP) is a component of the shelterin complex that protects telomeric DNA and preserves chromosome stability. In addition to its telomeric function, accumulating evidence indicates that mammalian RAP1 also exerts multiple extra-telomeric functions. Notably, RAP1 has been reported to regulate the NF-<i>κ</i>B signaling pathway and to function as a transcriptional regulator, suggesting potential roles in tumorigenesis. In this study, we found that RAP1 expression was significantly upregulated in hepatocellular carcinoma (HCC) cells. Functional analyses demonstrated that RAP1 promoted malignant phenotypes in HCC through a non-telomeric mechanism. In cellular models, RAP1 overexpression enhanced cell proliferation while suppressing senescence and apoptosis, whereas RAP1 knockdown produced the opposite effects. Mechanistically, RAP1 functioned as an upstream activator of the NF-<i>κ</i>B signaling cascade, resulting in increased phosphorylation of the p65 subunit and upregulation of downstream targets, including <i>IL-1β</i> and <i>BCL-2</i>. Importantly, the oncogenic activity of RAP1 was shown to be dependent on NF-<i>κ</i>B signaling in vivo, as pharmacological inhibition of NF-<i>κ</i>B significantly suppressed RAP1-driven tumor growth in a xenograft model. Collectively, these findings reveal a previously unrecognized role for RAP1 in promoting HCC progression through activation of NF-<i>κ</i>B signaling and identify the RAP1/NF-<i>κ</i>B axis as a potential therapeutic target for HCC.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148455898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Half-Life as a Therapeutic Design Axis: Targeting Short-Lived lncRNAs With Antisense Oligonucleotides","authors":"Hidenori Tani","doi":"10.1002/iub.70122","DOIUrl":"10.1002/iub.70122","url":null,"abstract":"<div>\u0000 \u0000 <p>Engineering RNA stability has become a cornerstone of modern therapeutics, almost entirely in one direction: mRNA vaccines established <i>stabilisation</i> of exogenous transcripts as a powerful design axis. The symmetric operation—<i>exploitation</i> of instability in endogenous targets—has been comparatively underexplored. We argue that target RNA half-life is an underused but quantitatively consequential design parameter for antisense oligonucleotide (ASO) therapeutics, and that short-lived long noncoding RNAs (lncRNAs) are a particularly attractive target class. Under sustained ASO dosing, the time to a new steady state is set by the sum of the target's own decay rate and the ASO-induced decay rate, so—for a given depth of knockdown—endogenous half-life becomes a major determinant of pharmacodynamic onset alongside ASO potency and delivery, most directly for RNase H-dependent gapmers; we treat the resulting first-order relationships as a qualitative design heuristic rather than a quantitative pharmacokinetic/pharmacodynamic model. Two back-to-back 2012 surveys—BRIC-seq in human HeLa and actinomycin-D microarray in mouse Neuro-2a—yielded similar median lncRNA half-lives of 3.4 and 3.5 h, with a short-lived fraction we term short-lived noncoding transcripts (SLiTs; <i>t</i>_1/2 &lt; 4 h). SLiTs include several disease-relevant regulators (GAS5, NEAT1, CDKN2B-AS1/ANRIL, HOTAIR, TUG1); their rapid turnover supports fast onset, reversibility and tight titratability. We (i) develop a kinetic framework for how target half-life shapes ASO pharmacodynamic onset, (ii) survey the cross-species half-life landscape, (iii) propose a <i>decay-pathway-aware ASO design</i> framework aligning modality choice with endogenous decay machinery, (iv) re-read representative clinical ASO cases (nusinersen, tofersen, tominersen, MALAT1 ASOs) through the half-life lens, and (v) outline a half-life-aware preclinical roadmap. Treating half-life symmetrically—engineered up in vaccine RNAs, exploited downward in endogenous targets—highlights a largely unoccupied design space for next-generation oligonucleotide therapeutics.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148421251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ALKBH4 Promotes Osteogenesis via Epigenetic Regulation of BMP2-Wnt/β-Catenin Signaling in Cervical Spine OPLL","authors":"Haiyan Qiu,&nbsp;Yanze Lin,&nbsp;Xun Wang,&nbsp;Luo Chen,&nbsp;Xinji Chen,&nbsp;Fabo Feng","doi":"10.1002/iub.70121","DOIUrl":"https://doi.org/10.1002/iub.70121","url":null,"abstract":"<div>\u0000 \u0000 <p>DNA N6-methyladenine (6 mA) has recently been recognized as a novel epigenetic modification, with ALKBH4 identified as a specific demethylase. However, the role of ALKBH4 and DNA 6 mA in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL) remains unclear. Tissue samples from OPLL patients and normal posterior longitudinal ligaments were collected, and ligament fibroblastic cells (LFCs) were isolated from OPLL tissues using primary culture. The expression and functional relevance of ALKBH4 in OPLL were investigated through reverse transcription quantitative polymerase chain reaction and western blot analyses. Osteogenic potential was further assessed using alizarin red S staining and alkaline phosphatase activity assays. Methylation status was evaluated by enzyme-linked immunosorbent assay and chromatin immunoprecipitation. Furthermore, the regulatory role of ALKBH4 in LFC ossification was investigated through the bone morphogenetic protein 2 (BMP2) and Wnt/β-catenin pathways. ALKBH4 expression was significantly elevated in both OPLL tissues and LFCs, whereas global 6 mA levels and BMP2-associated 6 mA were reduced. Overexpression of ALKBH4 promoted the ossification of LFCs, while its knockdown suppressed osteogenesis. ALKBH4-mediated DNA demethylation at the 6 mA site facilitated Yin Yang 1 (YY1) binding to the BMP2 promoter, enhancing BMP2 transcription and driving ossification. Silencing of BMP2, Wnt/β-catenin, or YY1 attenuated the pro-ossification effects of ALKBH4. Furthermore, the mutation that affects the action of ALKBH4 at the 6 mA site fails to induce the osteogenic effect of LFC. These findings demonstrate that ALKBH4 regulates OPLL progression by modulating BMP2 and Wnt/β-catenin signaling and by promoting BMP2 transcription through site-specific demethylation in human OPLL tissues and primary LFCs. ALKBH4 may therefore represent a promising therapeutic target for the management of OPLL.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 7","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Sequence Deep Learning Delivers Crystal-Quality Models of Covalent K-Ras G12 Hotspot Complexes","authors":"Sungwon Jung,&nbsp;Qinheng Zheng,&nbsp;Kevan M. Shokat","doi":"10.1002/iub.70108","DOIUrl":"https://doi.org/10.1002/iub.70108","url":null,"abstract":"<p>Structure-based design of covalent drugs has achieved tremendous success by understanding and leveraging the three-dimensional interactions between small-molecule drug candidates and their protein targets. However, this approach traditionally relies on high-resolution co-complex structures obtained by X-ray crystallography, NMR, or cryo-EM, methods that are time-consuming and resource-intensive. Here we show that Chai-1, a publicly available structure prediction tool that accepts user-defined ligands, is able to accurately predict covalent K-Ras(G12C) complexes without using a multiple sequence alignment (MSA). Chai-1 yields pocket-aligned RMSDs &lt; 2 Å for chemically diverse K-Ras(G12C) inhibitors, ranging from ARS-853 to BBO-8520. In addition to the conventional acrylamide-based covalent K-Ras(G12C) inhibitors, Chai-1 with a covalent-bond restraint successfully reproduced the binding poses of covalent K-Ras(G12D) and K-Ras(G12S) inhibitors, while showing limitations in capturing chemical details such as accounting for leaving groups, bond properties, and stereochemistry. Chai-1 also provides ~40-fold higher throughput than state-of-the-art AlphaFold3 while maintaining comparable pose accuracy. Together, these findings establish Chai-1 as an accessible and computationally efficient tool for covalent protein-ligand co-complex structure prediction, with its covalent-restraint mode offering a unique solution to accelerate covalent drug discovery, especially for challenging targets beyond cysteine.</p>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148238172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of PCSK9-Mediated Macrophage Activation via the CAP1/NF-κB Pathway in CAWS-Induced Kawasaki Disease Vasculitis","authors":"Hao Zhang,&nbsp;Dujuan Shuai,&nbsp;Miaohua Ruan,&nbsp;Mao Wu,&nbsp;Linlin Wang,&nbsp;Maoping Chu,&nbsp;Xing Rong","doi":"10.1002/iub.70119","DOIUrl":"10.1002/iub.70119","url":null,"abstract":"<div>\u0000 \u0000 <p>Proprotein convertase subtilisin/kexin type 9 (PCSK9) acts as a pleiotropic modulator of inflammation. This study aimed to investigate the role and underlying mechanism of PCSK9 in Kawasaki disease (KD)-associated vasculitis. A <i>Candida albicans</i> water-soluble fraction (CAWS)-induced murine vasculitis model (<i>n</i> = 5–8 mice per group) and CAWS-stimulated RAW 264.7 macrophages (<i>n</i> = 3–8 independent experiments) were used. PCSK9 was pharmacologically inhibited in vivo with SBC-115076 and in vitro with PF-06446846. Vascular pathology, inflammatory markers, macrophage polarization, and signaling pathways were evaluated using hematoxylin–eosin (H&amp;E) staining, immunofluorescence (IF), Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and RNA sequencing (RNA-seq). CAP1 overexpression was performed via lentiviral infection in RAW 264.7 cells to further validate its functional role. PCSK9 expression was significantly upregulated (two-fold) in the coronary arteries of CAWS-treated mice, and PCSK9 was predominantly co-localized with macrophages. Pharmacological inhibition of PCSK9 attenuated coronary arteritis, reduced the inflammatory infiltrate fraction by 54%, attenuated systemic inflammation, and decreased cardiac macrophage infiltration by 89%. In vitro, PCSK9 blockade suppressed CAWS-induced M1 macrophage polarization, as shown by reduced expression of the markers CD86 (by 96%) and iNOS (by 60%), and decreased secretion of the pro-inflammatory cytokines TNF-α (by 80%), IL-1β (by 86%), and IL-6 (by 89%). Transcriptomic analysis identified the NF-κB pathway as a key downstream signaling pathway. Mechanistically, PCSK9 inhibition downregulated CAP1 (adenylyl cyclase-associated protein 1) expression by 64% and suppressed NF-κB p65 nuclear translocation by 91% in macrophages. Importantly, CAP1 overexpression reversed the inhibitory effects of PCSK9 blockade on p65 nuclear translocation, M1 polarization, and inflammatory cytokine production. PCSK9 promotes KD-like vasculitis by activating the CAP1-mediated NF-κB pathway in macrophages, thereby driving pro-inflammatory responses. Pharmacological inhibition of PCSK9 attenuates vascular immunopathology, highlighting PCSK9 as a potential therapeutic target for KD.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148225435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hormesis and the Golden Ratio: Toward a Universal Estimator of Adaptive Capacity","authors":"Evgenios Agathokleous","doi":"10.1002/iub.70118","DOIUrl":"10.1002/iub.70118","url":null,"abstract":"<div>\u0000 \u0000 <p>Hormesis represents a universal feature of biological plasticity across species and environmental contaminants. Here I propose that the maximum stimulatory peak converges upon the golden ratio (<i>φ</i> = 1.618), representing a 61.8% increase above baseline, a value embedded within the empirically observed 30%–60% range but offering mathematical precision for a unifying quantitative reference. I further hypothesize that the internal architecture of the hormetic zone may follow the complementary proportion of <i>φ</i> (0.382), with the rising phase occupying the smaller fraction (steep ascent) and the falling phase the larger fraction (gradual decline), reflecting natural selection for rapid threat response followed by sustained benefit. This framework positions the golden ratio as a potential evolutionary optimum, a Pareto-efficient allocation where further investment yields diminishing returns. While the dose-width to toxicity remains variable and context-dependent, the peak magnitude may reveal a fundamental constraint on the adaptive capacity of life. Testing this hypothesis requires systematic meta-analysis of existing databases and targeted experiments manipulating resource availability, genetic background, and evolutionary history.</p>\u0000 </div>","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"78 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148198896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}