Biochimica Et Biophysica Acta[JOURNAL]
Sun
200 papers
New insights into the multifaceted role of eryptosis in metabolic and cardiovascular diseases.
Tkachenko A, Quintanar-Escorza MA, Tryfonyuk L … +1 more , Havranek O
Biochim Biophys Acta Mol Cell Res · 2026 Jun · PMID 42155670 · Publisher ↗
Cardiovascular diseases (CVDs) remain a global medical and social burden with high morbidity and mortality rates worldwide. CVDs are strongly linked to thrombosis, anemia, endothelial dysfunction, or inflammation. A grow...
Cardiovascular diseases (CVDs) remain a global medical and social burden with high morbidity and mortality rates worldwide. CVDs are strongly linked to thrombosis, anemia, endothelial dysfunction, or inflammation. A growing body of evidence indicates that eryptosis, a regulated cell death of mature erythrocytes, plays an emerging role in CVDs by contributing to the above-mentioned pathogenetic links. In this review, we summarize the current knowledge of the key signaling pathways involved in eryptosis execution, highlight the pathophysiological role of eryptosis in CVDs and related metabolic disorders (including metabolic syndrome, diabetes mellitus, atherosclerosis, ischemic heart disease, or heart failure), identify the key molecular drivers of eryptosis in cardiovascular pathology, and shed light on the potential detrimental effects of enhanced eryptosis in CVDs. Identification of eryptosis-related complications of CVDs might provide novel insights into preventive and therapeutic strategies. Enhanced eryptosis in metabolic and cardiovascular pathology contributes to anemia via the accelerated clearance of eryptotic red blood cells (RBCs). Thrombogenic effects of eryptosis in CVDs are mediated by phosphatidylserine (PS)-mediated thrombin generation, interactions with platelets, and generation of coagulation-promoting PS-expressing RBC-derived microvesicles. Eryptosis-induced endothelial dysfunction is at least partly attributed to PS/CXCL16-mediated adhesion of eryptotic cells to endothelial cells (ECs), consequent uptake of eryptotic cells by ECs, and induction of their ferroptosis. On the other hand, enhanced eryptosis might have a dual role in the regulation of inflammation in CVDs. Phagocytosis of eryptotic cells reprograms macrophages to gain the pro-resolution phenotype. However, eryptosis triggers pro-inflammatory ferroptosis of ECs and immune cells at the same time.
Role of HMGB1 in tumors and its targeted therapy.
Chu J, Dong C, Li B
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42144084 · Publisher ↗
High-mobility group box 1 (HMGB1), a protein with context-dependent pro- and anti-tumor functions, is expressed in tumor cells, tumor-associated macrophages, tumor-associated neutrophils, cancer-associated fibroblasts, a...
High-mobility group box 1 (HMGB1), a protein with context-dependent pro- and anti-tumor functions, is expressed in tumor cells, tumor-associated macrophages, tumor-associated neutrophils, cancer-associated fibroblasts, and T cells within the tumor microenvironment. The identity of HMGB1 has undergone a transformation from a nuclear architectural protein to a secreted damage-associated molecular pattern with pivotal roles in inflammation and cancer. The heterogeneity of HMGB1 stems from the diversity of post-translational modifications, proteolytic cleavage and lysis, partial independence of domain functions, differences in source tissues and cells, concentration-dependent effects, spatiotemporal distribution and dynamics, and functional diversity. This review summarizes the roles and molecular mechanisms of nuclear, cytoplasmic, and extracellular HMGB1 derived from different cells in tumor progression, its targeted therapy, and its application value as a biomarker, highlighting the regulation of HMGB1 and the downstream signaling pathways of HMGB1. HMGB1 mainly exerts pro-tumor effects during tumor progression via multiple downstream pathways (MAPK, NF-κB, PI3K/AKT, Wnt, STAT3, etc.), while its subtle induction of cell death and enhancement of the immune response demonstrate moderate anti-tumor effects. HMGB1-mediated immune crosstalk regulates the proliferation, growth, migration, invasion, and chemoresistance of tumors. A comprehensive investigation of the spatiotemporal dynamics of HMGB1 and its underlying molecular regulatory mechanisms using cutting-edge technologies, including single-cell RNA sequencing, spatial transcriptomics, and real-time live-cell imaging, will facilitate the development of precise, mechanism-informed therapeutic interventions. Given the multifaceted challenges posed by tumor heterogeneity, the dual pro- and anti-tumor functions of HMGB1, and the limitations of targeting technologies, HMGB1-targeted strategies hold substantial promise for clinical translation.
Thermotropic and barotropic phase behavior of phospholipid bilayers: A thermodynamic phase-diagram perspective incorporating modular lipid architecture.
Tamai N, Goto M, Matsuki H
Biochim Biophys Acta Biomembr · 2026 Jul · PMID 42142796 · Publisher ↗
Understanding how lipid bilayer phase behavior responds to temperature and pressure is essential for elucidating membrane stability and adaptability under diverse environmental conditions. In this review, thermotropic an...
Understanding how lipid bilayer phase behavior responds to temperature and pressure is essential for elucidating membrane stability and adaptability under diverse environmental conditions. In this review, thermotropic and barotropic phase behavior of hydrated phospholipid bilayers is systematically organized using temperature (T)-pressure (p) phase diagrams as a central framework. After outlining fundamental bilayer phase states and transitions using dipalmitoylphosphatidylcholine as a reference system, general features and thermodynamic interpretation of T-p phase diagrams are summarized to provide a unified basis for comparison. The main focus of this review is a modular structural analysis of phospholipid molecules, in which bilayer phase behavior is discussed in terms of three intrinsic molecular modules: the hydrophobic chain region (C module), the linkage connecting hydrophobic chains to the glycerol backbone (L module), and the polar head group (H module). Variations in these modules reshape T-p phase diagrams by altering intermolecular interactions within the bilayer core, backbone region, and membrane interface. Phase-boundary positions are highly sensitive to molecular structure, whereas dT/dp values primarily reflect the nature of the transition and, in specific cases, interfacial conditions such as head-group charge and salt concentration. Ligand effects, including solvent substitution, membrane-active molecules, and cholesterol, are discussed as extrinsic modifiers that regulate bilayer phase behavior by tuning thermodynamic contributions without altering transition mechanisms. Finally, the coexistence of structural diversity and conserved modular architecture in phospholipids is highlighted, and future perspectives based on chemically designed lipids with modified modular arrangements are discussed within the emerging framework of chemical lipidology.
Full-length SARS-CoV-2 envelope protein adopts an interfacial topology in lipid bilayers.
Morris AK, Wardrip L, Sahu ID … +1 more , Lorigan GA
Biochim Biophys Acta Biomembr · 2026 May · PMID 42142795 · Publisher ↗
The envelope protein is essential for the replication of coronaviruses. Several structures of the envelope protein of the SARS-CoV-2 and the closely related SARS viruses are available. However, an experimental structure...
The envelope protein is essential for the replication of coronaviruses. Several structures of the envelope protein of the SARS-CoV-2 and the closely related SARS viruses are available. However, an experimental structure of the entire full-length protein in a native lipid environment has not been determined. In addition, significant structural differences exist between published models, and the conformation adopted by the C-terminal domain is only partially understood. CW-EPR power saturation and EPR lineshape analysis of 15 different labeled sites were carried out on the full-length envelope protein of SARS-CoV-2 in POPC/POPG vesicles to determine the membrane topology. In conjunction with coarse-grained molecular dynamics, the results support a model where the C-terminal domain helices as well as the N-terminal domain are in direct contact with the lipid headgroups of the ER cytoplasmic leaflet of the membrane.
Reshaping tumor immunity by targeting SUMOylation: A novel immunotherapeutic strategy.
Yi M, Wu X, Guo P … +2 more , Yu X, Li W
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42142669 · Publisher ↗
SUMOylation, a reversible post-translational modification mediated by Small Ubiquitin-like Modifier (SUMO) proteins, is fundamental to regulating transcriptional programs, particularly within the nucleus. Accumulating ev...
SUMOylation, a reversible post-translational modification mediated by Small Ubiquitin-like Modifier (SUMO) proteins, is fundamental to regulating transcriptional programs, particularly within the nucleus. Accumulating evidence indicates that SUMOylation is a critical modulator of immune signaling and inflammatory responses, with profound implications for infections, autoimmune disorders, and oncogenesis. In the context of the tumor immune microenvironment(TIME), aberrant SUMOylation activity orchestrates an immunosuppressive landscape by directly altering the function of key transcription factors in both innate and adaptive immune cells. Consequently, pharmacological inhibition of the SUMO pathway, exemplified by the first-in-class inhibitor TAK-981, has emerged as a promising therapeutic strategy. Such inhibitors can reverse immune suppression by enhancing type I interferon signaling, augmenting antigen presentation, and reinvigorating anti-tumor immunity. In this review, we synthesize current understanding of how SUMOylation governs the function and polarization of critical immune cells within the TIME, and explore the therapeutic potential of SUMO-targeting inhibitors in cancer treatment, aiming to provide novel theoretical insights and innovative strategies to advance cancer therapy.
Emerging concepts, hot topics, and open questions in today's pancreatic cancer research.
Keber C, Schmitt M, Visekruna A … +7 more , Brichkina A, von Strandmann EP, Bartsch JW, Huber M, Bauer UM, Gress TM, Lauth M
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42142668 · Publisher ↗
Despite intense research, pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies to date. The low 5-year survival rate of currently 8-10% has only marginally improved over the last years, nec...
Despite intense research, pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies to date. The low 5-year survival rate of currently 8-10% has only marginally improved over the last years, necessitating novel approaches and a thinking "outside the box". We as translational basic and medical scientists working in a clinical research unit on tumor-stroma interactions in PDAC (the DFG-funded CRU325) have sought to identify emerging concepts in current pancreatic cancer research. We have addressed recent developments and open questions, covering a wide spectrum of topics, including clinical treatment, lifestyle, the tumor microenvironment, drug targeting, vaccination, and the microbiome. This selection of topics is highly personal and does not claim to be complete, yet it represents those areas that we believe may contribute to relevant developments in the near future. In our review, we not only briefly describe the state of the art but also pinpoint the potential of recent advances, while not ignoring current contradictions or uncertainties. Taken together, we provide our subjective view on upcoming topics in today's PDAC research landscape.
Sexual dimorphism and estrogens in neuroendocrine neoplasms.
Strachowska M, Jacenik D
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42142667 · Publisher ↗
Neuroendocrine neoplasms (NENs) belong to a heterogeneous group of tumors with diverse morphological and biological features. Evidence indicates that patients with NENs show sexual dimorphism, which may influence not onl...
Neuroendocrine neoplasms (NENs) belong to a heterogeneous group of tumors with diverse morphological and biological features. Evidence indicates that patients with NENs show sexual dimorphism, which may influence not only disease incidence but also its course and treatment response. The role of estrogens and estrogen receptors (ERs) has been extensively described in breast and endometrial cancer, although their importance in the pathophysiology of NENs remains poorly understood. In this review, we discuss current knowledge regarding the impact of estrogens and their receptors on the progression of NEN. We also elaborated the expression patterns of ERs in different NEN subtypes. Considering epidemiological differences between sexes, we analyze gender relationships in ER expression and NEN progression. Finally, we present available clinical data on the therapeutic potential of ER in NENs. Understanding estrogen roles in NENs may contribute to elucidate gender differences in the course of the disease and open the way to the design of new personalized therapies.
Pretreatment of ADSCs with resveratrol-functionalized selenium nanoparticles alleviate CCl-induced liver fibrosis in mice.
Liu S, Zhang Z, Luo D … +7 more , Wen F, Zhu X, Chen X, Zhang T, Feng J, Hou L, Liu Y
Biochim Biophys Acta Mol Basis Dis · 2026 Aug · PMID 42142461 · Publisher ↗
BACKGROUND: Liver fibrosis (LF) is an abnormal repair reaction after chronic liver injury. Currently, adipose-derived mesenchymal stem cells (ADSCs) are widely used in the treatment of liver diseases. However, the therap...
BACKGROUND: Liver fibrosis (LF) is an abnormal repair reaction after chronic liver injury. Currently, adipose-derived mesenchymal stem cells (ADSCs) are widely used in the treatment of liver diseases. However, the therapeutic effect of ADSCs is affected by the damaged microenvironment. In this study, a resveratrol-functionalized nano‑selenium (Res@SeNPs) formulation was prepared to investigate whether Res@SeNPs pretreatment can enhance the therapeutic effect and alter the potential mechanism of ADSCs in carbon tetrachloride (CCl) -induced LF in mice. METHODS: Res@SeNPs were prepared and ADSCs pretreated with Res@SeNPs were cocultured with CCl-injured BRL-3A cells in vitro. In vivo, ADSCs pretreated with Res@SeNPs were injected into the tail vein of a CCl-induced LF mouse model. RESULTS: Res@SeNPs were successfully prepared. In vitro, after coculture with BRL-3A cells, the function of damaged BRL-3A cells was improved. In vivo, Res@SeNPs-pretreated ADSCs effectively alleviated liver function damage and fibrosis in mice with LF. This may be related to the inhibition of oxidative stress, the reduction in apoptosis and the inhibition of the activation of the apoptosis signal-regulated kinase 1/c-Jun N-terminal kinase/p38 mitogen-activated protein kinase (ASK1/JNK/p38) pathway. CONCLUSION: Our study suggested that Res@SeNPs pretreatment can enhance the therapeutic effect of ADSCs on LF in mice, and in vivo findings indicated the potential mechanism of ADSCs, providing new ideas for the treatment of LF.
USP8/GPX4-based live-cell quantitative FRET imaging for ferroptosis drug screening.
Cai X, Wu Z, Xiao Z … +2 more , Zhuang G, Zhuang Z
Biochim Biophys Acta Mol Cell Res · 2026 Jun · PMID 42140526 · Publisher ↗
Targeting the functional interface between USP8 and GPX4 to disrupt ferroptosis defense represents a novel therapeutic strategy in cancer. Currently, there is a lack of drug screening models targeting the USP8/GPX4 inter...
Targeting the functional interface between USP8 and GPX4 to disrupt ferroptosis defense represents a novel therapeutic strategy in cancer. Currently, there is a lack of drug screening models targeting the USP8/GPX4 interaction. This study utilized human breast cancer cell lines as a research model and established a drug screening platform capable of real-time, quantitative detection of USP8/GPX4 interactions in live cells based on fluorescence resonance energy transfer (FRET) imaging technology. We first confirmed that USP8 promotes malignant growth in breast cancer cells. Using the USP8 inhibitor DUB-IN-2 as a positive control alongside key ferroptosis markers, we employed FRET technology to quantitatively assess the interaction efficiency (E) between USP8 and GPX4. Screening of candidate compounds revealed that treatment with ML162, RSL3, and sorafenib resulted in maximum FRET efficiencies (E) of 0.492, 0.483, and 0.503, respectively-significantly lower than that of control cells (0.548)-indicating effective disruption of USP8/GPX4 binding. This study successfully establishes a novel and efficient FRET-based drug screening model for targeting ferroptosis.
Matrix metalloproteinase-14 promotes LRP6 shedding in vascular smooth muscle cells and its expression is elevated in the tibial arteries from peripheral artery disease.
Chen HG, Gao D, Zeng GF … +10 more , Zhang GP, Yuan ZY, Pan DH, Qin YK, Lv ZY, Tan XB, Chen GT, Wang GQ, Zhang DW, Xia XD
Biochim Biophys Acta Gen Subj · 2026 Aug · PMID 42140397 · Publisher ↗
Vascular smooth muscle cells (VSMCs) dedifferentiation is a key driver of peripheral artery disease (PAD), a common complication of atherosclerosis. Although matrix metallopeptidase 14 (MMP14) has been implicated in prom...
Vascular smooth muscle cells (VSMCs) dedifferentiation is a key driver of peripheral artery disease (PAD), a common complication of atherosclerosis. Although matrix metallopeptidase 14 (MMP14) has been implicated in promoting VSMC dedifferentiation, the underlying mechanisms remain incompletely defined. Here, we demonstrate that MMP14 expression is markedly increased in PAD plaques, accompanied by elevated platelet-derived growth factor receptor-β (PDGFRβ) and reduced low-density lipoprotein receptor-related protein 6 (LRP6) levels, predominantly within VSMCs, compared with plaque-free arterial segments. Mechanistically, MMP14 selectively promoted LRP6 shedding without affecting LRP5 in VSMCs. Genetic or pharmacological inhibition of MMP14 increased LRP6 abundance, reduced PDGFRβ and SP1 expression, attenuated ERK phosphorylation, and suppressed VSMC proliferation and migration. In contrast, MMP14 overexpression produced opposite effects. Collectively, these findings indicate that MMP14 enhances VSMC proliferation and migration through modulation of the LRP6-PDGFRβ signaling axis.
The underexplored complexity of pancreatic cancer: Early dissemination and quiescence.
Kumar NK, Kaur AB, Batra SK … +1 more , Ponnusamy MP
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42134624 · Publisher ↗
Pancreatic cancer has been renowned for its aggressive nature and occasionally manifests periods of dormancy, presenting a perplexing challenge in studying disease progression. Despite surgery, many patients relapse due...
Pancreatic cancer has been renowned for its aggressive nature and occasionally manifests periods of dormancy, presenting a perplexing challenge in studying disease progression. Despite surgery, many patients relapse due to dormancy and chemoresistance, resulting in recurrence and death within a few years. Studies also suggest that pancreatic cancer disseminates early on, spreading to secondary organs with no evidence of disease. The lingering question is: how, where, and when does pancreatic cancer recur and spread? Herein, we explore evidence for clinically dormant pancreatic cancer cells, examining the roles of quiescence and stemness populations and their interactions with the tumor microenvironment. Understanding the molecular factors that control dormancy is crucial for addressing disease heterogeneity and offers opportunities for targeted interventions to enhance pancreatic cancer outcomes.
Mammalian mtDNA gene expression: Concepts learned from in vivo models.
Rubalcava-Gracia D, Larsson NG
Biochim Biophys Acta Mol Cell Res · 2026 Jun · PMID 42134553 · Publisher ↗
Mammalian mitochondrial DNA (mtDNA) expression is essential for oxidative phosphorylation (OXPHOS) and its in vivo regulation requires significant refinement. Here, we review key insights from mouse models carrying genet...
Mammalian mitochondrial DNA (mtDNA) expression is essential for oxidative phosphorylation (OXPHOS) and its in vivo regulation requires significant refinement. Here, we review key insights from mouse models carrying genetic modifications to the mtDNA expression machinery. While in vitro studies defined the basic machinery, mouse models reveal that mitochondrial transcription often exceeds immediate needs and may not be the primary rate-limiting step for OXPHOS biogenesis. Instead, mitochondria produce a transcript surplus regulated by nucleoid compaction and post-transcriptional stabilization. This apparent excess capacity is uncoupled from protein output under basal conditions but becomes critical during physiological stress or pathology. Using current and emerging genetic tools, researchers are now deciphering how regulatory layers coordinate to sustain systemic energy demands. These lessons highlight the importance of in vivo systems for identifying regulatory control points of mtDNA expression and developing targeted therapies for mitochondrial disorders.
Developmental DVE-1 programs ACT-5-dependent microvillar organization to preserve intestinal homeostasis in C. elegans.
Yang L, Liu J, Guo S … +7 more , Sun L, Zhang J, Hu X, Yang H, Yang X, Wang Z, Sun X
Biochim Biophys Acta Mol Basis Dis · 2026 Aug · PMID 42128188 · Publisher ↗
The intestinal epithelium balances nutrient absorption and barrier defense using its apical brush border. Disrupting this structure causes malabsorption and disease, but the transcriptional programs driving its formation...
The intestinal epithelium balances nutrient absorption and barrier defense using its apical brush border. Disrupting this structure causes malabsorption and disease, but the transcriptional programs driving its formation remain unclear. Here, we identify DVE-1-a homeobox transcription factor known for regulating the mitochondrial unfolded protein response (UPR)-as essential for intestinal lumen integrity and absorptive function in C. elegans. Intestine-specific depletion of DVE-1 during development (but not adulthood) causes severe lumen distension and bacterial accumulation. Although DVE-1 loss induces antibacterial gene expression, genetic analyses reveal that this excessive immune activation is a secondary consequence rather than the primary driver of the pathology. Instead, DVE-1 deficiency disrupts the apical cytoskeleton: ACT-5 (brush-border actin) is reduced and mislocalized. This structural collapse, accompanied by severe disruptions in apical endocytic trafficking, leading to shortened microvilli, aberrant endosomal dynamics, and defective peptide absorption, which can be partially rescued by ACT-5 restoration. Thus, DVE-1 has a developmental, non-canonical role in building the apical machinery required for epithelial homeostasis. By connecting a mitochondrial stress regulator to ACT-5-dependent microvillar organization, our work reveals how transcriptional control maintains intestinal structure-and offers mechanistic insight into microvillus inclusion diseases.
Neoantigen-driven personalized vaccines for breast cancer: Platforms, nano-delivery systems, and combination strategies.
Liu X, Liu J, Chao T … +2 more , Liu Q, Xiong H
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42128147 · Publisher ↗
Breast cancer (BC) is the most common malignancy among women globally. Despite significant advances, therapeutic resistance and tumor recurrence remain major clinical challenges. Personalized cancer vaccines have recentl...
Breast cancer (BC) is the most common malignancy among women globally. Despite significant advances, therapeutic resistance and tumor recurrence remain major clinical challenges. Personalized cancer vaccines have recently emerged as a promising strategy to induce durable, highly specific anti-tumor immune responses and improve long-term survival. However, challenges persist in neoantigen prediction, vaccine formulation, and practical implementation, which can hinder the overall effectiveness and widespread adoption of these personalized cancer vaccines. Ongoing technological advancements are expected to facilitate the development of more efficient and accessible personalized vaccines for BC. This review systematically summarizes recent progress in personalized BC vaccines, focusing on neoantigen identification, emerging vaccine platforms, nano-delivery systems, and subtype-specific vaccine strategies. It also discusses the pharmacological basis of these vaccines, including immune activation mechanisms, pharmacokinetic influences on efficacy, and mechanisms of vaccine resistance. Furthermore, we explore combination strategies integrating cancer vaccines with immune checkpoint inhibitors (ICIs), radiotherapy, and chemotherapy to overcome the immunosuppressive tumor microenvironment (TME) and enhance therapeutic efficacy. Ultimately, this review provides a comprehensive reference to guide future research and promote the clinical translation of personalized vaccine-based immunotherapies for breast cancer.
Expansion microscopy visualizes the photosystem distribution in Synechocystis cells.
Bos PR, Langlois-Legrand E, Wientjes E
Biochim Biophys Acta Bioenerg · 2026 May · PMID 42119961 · Publisher ↗
Photosynthesis in cyanobacteria relies on light capture by photosystem I (PSI), photosystem II (PSII) and the phycobilisome (PBS). Although these complexes are generally considered to be intermixed within the thylakoid m...
Photosynthesis in cyanobacteria relies on light capture by photosystem I (PSI), photosystem II (PSII) and the phycobilisome (PBS). Although these complexes are generally considered to be intermixed within the thylakoid membrane, several studies have suggested the presence of PSI- or PSII/PBS-enriched microdomains that may depend on environmental conditions. Here we applied cryo-Expansion Microscopy (cryo-ExM) to dark-adapted Synechocystis sp. PCC 6803 cells and achieved nanoscale resolution of thylakoid compartments and associated protein complexes. Cells were cryofixed, rehydrated at room temperature and physically expanded in a swellable hydrogel. By expanding cells 5.5-fold, we resolved individual thylakoid compartments in intact cells using confocal microscopy. Furthermore, immunolabeling allowed simultaneous localization of PSI, PSII and PBS within the expanded thylakoid network. Overall PSI, PSII, and PBS signals showed similar spatial distributions. However, PBS was excluded from the neck region between dividing cells, while PSI and PSII were present. These results establish cryo-ExM as a powerful method for visualizing cyanobacterial thylakoid membranes and mapping the distribution of key photosynthetic complexes, thereby complementing existing approaches for dissecting the spatial organization of photosynthesis.
Importance of N-terminal P2 residue in substrate recognition by bacterial DPP7 activity revealed by coefficient of variation in protease activity.
Sawase M, Shirakura K, Ohara-Nemoto Y … +5 more , Nishimata H, Kondo H, Ishikawa T, Fujita Y, Nemoto TK
Biochim Biophys Acta Gen Subj · 2026 Aug · PMID 42119793 · Publisher ↗
Dipeptidyl-peptidases (DPPs), including the S9-family DPP4 and DPP5 and the S46-family DPP7 and DPP11, are essential for growth of Porphyromonas gingivalis, a periodontopathic bacterium associated with systemic diseases....
Dipeptidyl-peptidases (DPPs), including the S9-family DPP4 and DPP5 and the S46-family DPP7 and DPP11, are essential for growth of Porphyromonas gingivalis, a periodontopathic bacterium associated with systemic diseases. DPPs release dipeptides in diverse combinations from peptidyl N-termini, thus enabling utilization of amino acids as carbon and energy sources. This study examined how DPP5 and DPP7 achieve division of labor despite both possessing preference for hydrophobic residues at the P1 and P2 substrate positions. To identify important positions of substrates that define the specificity of DPPs, the terms coefficient of variation in amino acid frequency and coefficient of variation in protease activity (CVA) are introduced, as the values increase when a substrate position more strongly affects enzyme activity. In particular, CVA was found useful for peptidases, such as DPPs, for which a limited number of substrates are available. Using HX-|-LD-4-methylcoumaryl-7-amide (MCA), XN-|-LD-MCA, and XN-|-SD-MCA (X = nine amino acids) as substrates, DPP5 and DPP7 exhibited higher CVA values at the P1 and P2 positions, respectively, than at their counter positions. Furthermore, least-squares method applied on the relationship between peptidase activity and hydrophobicity for 27 dipeptidyl-MCA substrates independently indicated the best fit for DPP5 at 100% P1 and 0% P2, and for DPP7 at 53% P1 and 47% P2. Both approaches showed that functional division of labor is achieved through the exclusive P1 preference of DPP5 and the unusual P2 significance for DPP7. These results also demonstrate the usefulness of CVA for evaluating positional effects of substrates in peptidase reactions.
Mitochondrial dysfunction redirects proton transport and energy homeostasis in Saccharomyces cerevisiae under variable pH and glucose conditions.
Anikyan L, Shirvanyan A, Guaragnella N … +1 more , Trchounian K
Biochim Biophys Acta Bioenerg · 2026 May · PMID 42114666 · Publisher ↗
Mitochondrial function is crucial for the regulation of energy metabolism, proton homeostasis, and stress adaptation in Saccharomyces cerevisiae. This study demonstrates the role of mitochondria in modulating cellular re...
Mitochondrial function is crucial for the regulation of energy metabolism, proton homeostasis, and stress adaptation in Saccharomyces cerevisiae. This study demonstrates the role of mitochondria in modulating cellular responses to varying extracellular pH (3.0, 5.0, 6.5) and glucose availability (0.5%, 2%). Results indicate that mitochondrial deficiencies in Δhap4 and ρ mutants selectively impair growth under acidic pH and 0.5% glucose conditions, whereas wild-type cells maintain pH-independent growth. Mitochondrial impairment redistributes intracellular H homeostasis regulation to plasma membrane and cytosolic H-ATPases in a glucose- and pH-dependent manner, with ρ cells exhibiting maximal reliance on non-mitochondrial ATPases. The N, N'- dicyclohexylcarbodiimide (DCCD)-sensitive J scales inversely with glucose availability, reflecting energy demand under nutrient limitation and acid stress. ρ cells exhibit the highest alcohol dehydrogenase activity to regulate the redox balance in response to non-functional mitochondria. The highest total H-ATPase activity measured in ρ cells at pH 6.5 and 0.5% glucose conditions, combined with proton flux data, indicates the upregulation of plasma membrane and cytosolic ATPases activity for maintaining proton motive force and intracellular pH due to a complete loss of FF-ATPase contribution. These results pave the way for the construction of robust S. cerevisiae yeast strains to varying glucose and extracellular pH conditions.
Eicosanoids in lung cancer: Mechanisms, metabolism, and therapeutic potential.
Park WH
Biochim Biophys Acta Mol Basis Dis · 2026 Aug · PMID 42114605 · Publisher ↗
Lung cancer is the leading cause of cancer-related mortality worldwide, and its pathogenesis is intricately associated with chronic inflammation and metabolic reprogramming. Eicosanoids, a diverse class of lipid mediator...
Lung cancer is the leading cause of cancer-related mortality worldwide, and its pathogenesis is intricately associated with chronic inflammation and metabolic reprogramming. Eicosanoids, a diverse class of lipid mediators derived predominantly from arachidonic acid (AA), are integral to both inflammatory and homeostatic processes. Moving beyond historical pathway-centric descriptions, this review synthesizes recent findings by structuring the eicosanoid cascade around key biological themes: metabolic adaptation, tumor heterogeneity, immune evasion, and therapy resistance across major lung cancer histologies, specifically non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). To overcome the fragmentation of pathway-based analyses, this review intimately links distinct lipid signaling networks into broader biological frameworks, specifically delineating how eicosanoids orchestrate innate versus adaptive immune suppression. This review critically evaluates emerging controversies, integrating the dualistic role of AA metabolism in ferroptosis and the paradoxical context- and dose-dependent effects of lipid mediators directly into the framework of therapeutic vulnerability. Salient findings underscore how specific eicosanoids-particularly the cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and thromboxane A2 (TXA2) axes-function as central coordinators of the tumor microenvironment (TME), promoting immune exclusion and resistance to modern immunotherapies. Conversely, protective mediators, such as prostacyclin (PGI2) and specialized pro-resolving mediators derived from omega-3 fatty acids, exhibit potent anti-neoplastic properties. By integrating multi-omics insights, spatial TME dynamics, and proposing a unified conceptual model, this review highlights how a nuanced understanding of eicosanoid interplay and its inherent biological uncertainties is imperative for identifying novel biomarkers and overcoming resistance in personalized lung cancer oncology.
Effects of low and moderate doses of ionizing radiation on colon carcinogenesis: Experimental models and current evidence.
Gomot M, Klokov D, Varès G
Biochim Biophys Acta Rev Cancer · 2026 May · PMID 42114593 · Publisher ↗
Millions of people are exposed annually to low and moderate doses of ionizing radiation (LMDR), mostly as a result of medical diagnostic procedures. These individuals may be at increased risk of developing colon cancer (...
Millions of people are exposed annually to low and moderate doses of ionizing radiation (LMDR), mostly as a result of medical diagnostic procedures. These individuals may be at increased risk of developing colon cancer (CC), as predicted by the linear no-threshold model used for radioprotection. However, risk estimates derived from epidemiological studies remain subject to considerable uncertainty, necessitating a better mechanistic understanding of how LMDR may contribute to CC development. This review examines available experimental models for CC research and current evidence describing the effects of LMDR on colonic (and relevant intestinal) tumor development, including effects on cell proliferation, stemness, epigenetic modifications and oxidative stress, and their relevance for CC risk estimation. The review highlights the complex roles LMDR may play in colon carcinogenesis, underscores knowledge gaps and suggests priorities for future studies, with the overarching goal of improving our understanding of LMDR effects on colon cancer.
CRUMBS-associated mutations in Retinitis Pigmentosa and its impact on molecular scaffolding.
Khan S, Siddique YH
Biochim Biophys Acta Proteins Proteom · 2026 Jul · PMID 42107829 · Publisher ↗
The death of photoreceptors is a primary driver of retinal degenerative diseases, leading to irreversible vision loss. In Retinitis Pigmentosa (RP), a wide spectrum of mutations has been identified. Among these, the Crum...
The death of photoreceptors is a primary driver of retinal degenerative diseases, leading to irreversible vision loss. In Retinitis Pigmentosa (RP), a wide spectrum of mutations has been identified. Among these, the Crumbs (CRB) family of proteins, comprising CRB1, CRB2, and CRB3, plays a critical role in maintaining retinal homeostasis. The distribution of CRB mutations indicates population-specific variations, which may be influenced by factors such as founder effects, consanguinity, and geographic isolation. These findings suggest that genetic diagnostics and therapeutic strategies could benefit from considering population diversity. However, genotype-phenotype correlations remain complex, suggesting a modulatory role for genetic modifiers and environmental factors. Dysfunction of the CRB proteins disrupts apicobasal polarity of Retinal Pigment Epithelia (RPE) and photoreceptors, weakening their interaction and impairing phototransduction. This review highlights how mutations in conserved domains, especially the Epidermal Growth Factor (EGF)-like and Laminin G-like regions, compromise structural integrity and trigger degenerative cascades, establishing them as critical biomarkers and promising therapeutic targets for retinal degenerations.
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