bims-celmim Biomed News
on Cellular and mitochondrial metabolism
Issue of 2026–06–21
seventeen papers selected by
Marc Segarra Mondejar, AINA
  1. The pyruvate transporter hermes regulates autophagy and health by modulating ROS production.
  2. Intermediate accumulated upon interruption of fatty acid oxidation flux promotes tumoral ferroptosis and improves immunotherapy.
  3. Mitochondrial dynamics and T cells immunity in cancer.
  4. The competition of amino acid among tumors, tumor-associated macrophages and T cells based on metabolic reprogramming.
  5. Interdependent roles of PKM2 in photoreceptors and RPE: implications for retinal degeneration.
  6. Mitochondrial potassium channels: mitochondria-specific mechanism of regulation.
  7. The role of NAD+ metabolic reprogramming in colorectal cancer chemoresistance: mechanistic insights, clinical translation challenges and opportunities.
  8. Arginine metabolism supports de novo pyrimidine biosynthesis to block DNA damage and maintain Epstein-Barr virus latency.
  9. Messenger RNA-encoded reporters for monitoring cellular stress and bioenergetics.
  10. Pancreatic islet α cell function and proliferation require the arginine transporter SLC7A2.
  11. Lysosome-derived methylated arginine is a signalling metabolite controlling the lipidome.
  12. Chemigenetic fluorescent biosensors in biological imaging - New trends and advances.
  13. Aging and metabolism contribute separately to brain-body health.
  14. A single-vesicle fluorescence microscopy platform to quantify phospholipid scrambling.
  15. Mitochondria and brain aging: From cell-specific dysfunction to intercellular cooperation.
  16. LiMeNEx: an interactive webserver on lipid biochemical gene-regulatory network.
  17. Glycolytic reprogramming in ovarian cancer: mechanisms, immune crosstalk, and therapeutic implications.
  1. Cell Rep. 2026 Jun 19. pii: S2211-1247(26)00652-2. [Epub ahead of print]45(7): 117574
    The pyruvate transporter hermes regulates autophagy and health by modulating ROS production.
    Panagiotis D Velentzas, Fei Chai, Eric H Baehrecke.
      Autophagy is a catabolic process that degrades cytoplasmic materials and is controlled by nutrient availability and signaling. The plasma membrane-associated pyruvate-solute carrier hermes (hrm) is required for regulation of the mechanistic target of rapamycin (mTOR) signaling and the activation of autophagy during development. Here, we screen for pyruvate-influencing genes that suppress the hrm mutant phenotype. We show that the inhibitory effect of hrm loss on autophagy depends on pyruvate transport into mitochondria and the Krebs cycle. Loss of hrm results in an increase in reactive oxygen species (ROS), and attenuation of the increase in ROS is sufficient to suppress the effects of hrm loss on autophagy and mTOR signaling. Importantly, we show that in adult animals, loss of hrm results in decreased lifespan, with defects in autophagy in intestine tissues. These results link a plasma membrane pyruvate carrier to mitochondrial pyruvate metabolism, ROS, autophagy, and organismal health.
    Keywords:  CP: cell biology; CP: metabolism; Drosophila; autophagy; development; hermes; metabolism; pyruvate; reactive oxygen species
    DOI:  https://doi.org/10.1016/j.celrep.2026.117574
  2. Nat Commun. 2026 Jun 17.
    Intermediate accumulated upon interruption of fatty acid oxidation flux promotes tumoral ferroptosis and improves immunotherapy.
    Yuhan Zhou, Jing Li, Fangfang Liu, Yuan Gao, Songlin Yin, Liguo Yang, Xiaoxiao Li, Junhong Lin, Yan Li, Haotian Shang, Xiang Cheng, Tengfei Chao, Qian Chu, Fujia Lu, Weimin Wang.
      Therapeutic strategies targeting cancer metabolism are advancing rapidly. However, perturbing distinct nodes within the same metabolic pathway often yields divergent outcomes. Ferroptosis, a metabolic cell death driven by lipid peroxidation, has garnered attention for potentiating antitumor immunity. Here, we demonstrate that interruption of fatty acid oxidation (FAO) at hydroxyacyl-CoA dehydrogenase (HADHA) node promotes tumoral ferroptosis, whereas targeting upstream enzymes does not. HADHA inhibition causes accumulation of hydroxylated C18 (C18-OH) acylcarnitine to exacerbate mitochondrial lipid peroxidation. In vivo, HADHA ablation or acylcarnitine C18-OH supplementation suppresses tumor growth, enhances antitumor T-cell immunity, and potentiates PD-1 blockade therapy. Clinically, elevated plasma acylcarnitine C18-OH correlates with improved prognosis and immunotherapy response in lung cancer patients. Trimetazidine, an approved anti-ischemic drug and HADHA inhibitor, similarly delays tumor progression and augments immunotherapy. Together, our findings identify HADHA as a ferroptosis regulator and offer a clinically actionable strategy to enhance ferroptosis and immunotherapy through metabolic intervention.
    DOI:  https://doi.org/10.1038/s41467-026-74430-0
  3. Biochem Biophys Rep. 2026 Sep;47 102659
    Mitochondrial dynamics and T cells immunity in cancer.
    Xiaomei Li, Minghui Zhang, Yan Wang, Muhan Li, Tianzhen Wang, Xi Liu.
      Mitochondria are dynamic organelles that continuously adapt their number, morphology, and subcellular distribution in response to physiological and pathological stimuli. This plasticity is governed by a set of highly coordinated processes-collectively termed mitochondrial dynamics-including fusion, fission, mitophagy, and transport. Mitochondrial dynamics are essential for regulating cellular energy metabolism, proliferation, differentiation, and migration. Accumulating evidence highlights the critical role of mitochondrial dynamics in anti-tumor immunity, while their dysregulation contributes to immune evasion in cancer. In this review, we systematically outline how mitochondrial dynamics regulate the key stages of the T-cell immune response-from activation and differentiation to tumor infiltration, and finally to effector-mediated recognition and elimination of cancer cells-and elucidate the multifaceted mechanisms by which tumor cells suppress T-cell immunity through the regulation of mitochondrial dynamics. We aim to provide readers with an integrated conceptual framework, point toward future directions for translating fundamental insights into novel "metabolism-immunity" combination therapies, and thereby offer a theoretical foundation and strategic perspective for overcoming current bottlenecks in tumor immunotherapy.
    Keywords:  Cancer; Metabolic reprogramming; Mitochondria; Mitochondrial dynamics; T cell immunity
    DOI:  https://doi.org/10.1016/j.bbrep.2026.102659
  4. iScience. 2026 Jun 19. 29(6): 116253
    The competition of amino acid among tumors, tumor-associated macrophages and T cells based on metabolic reprogramming.
    Chenyang Xianyu, Yuxiao Song, Ci Zhao, Qian Min, Zhixu Wang, Mingbo Zhang, Bicheng Zhang.
      Amino acids are important nutrients in the process of tumor proliferation. Dysregulated amino acid metabolism profoundly influences tumor growth and immune cell function. Within the tumor microenvironment (TME), metabolic reprogramming of amino acids modulates the polarization of tumor-associated macrophages (TAMs) and the differentiation of T cells, processes intimately linked to tumor immune evasion. Meanwhile, metabolic reprogramming leads to amino acid competition between tumor cells and immune cells, particularly TAMs and T cells. To meet their own amino acid needs, tumors carry out a series of optimized metabolic strategies by expressing specific enzymes, cytokines, and amino acid transporters, and so forth promoting the formation of an immunosuppressive microenvironment and hindering anti-tumor immunity. Notably, this metabolic competition may exhibit spatial heterogeneity and temporal dynamics. Given the central role of amino acid metabolism in tumor progression and immune evasion, targeting key metabolic pathways represents a promising therapeutic strategy for cancer treatment.
    Keywords:  Cancer; Cancer systems biology; Human metabolism; Immune response
    DOI:  https://doi.org/10.1016/j.isci.2026.116253
  5. Cell Death Dis. 2026 Jun 19.
    Interdependent roles of PKM2 in photoreceptors and RPE: implications for retinal degeneration.
    Ammaji Rajala, Rahul Rajala, Larissa J Trevino, Tyler M Black, Gennadiy Moiseyev, Michael Kinter, Raju V S Rajala.
      Pyruvate kinase M2 (PKM2) functions as both a glycolytic enzyme and a transcriptional co-activator that coordinates metabolism and cell survival. Here, we define the developmental timing, cellular distribution, and physiological role of PKM isoforms in the mouse retina. PKM2 expression begins at postnatal day 2, preceding PKM1, and is highly enriched in photoreceptors, whereas PKM1 predominates in retinal ganglion cells. Conditional deletion of PKM2 in the retina, rods, or retinal pigment epithelium (RPE) demonstrated that PKM2 is essential for maintaining retinal structure and function. Loss of PKM2 impaired glycolytic activity, decreased ATP generation, and disrupted metabolic balance, leading to cellular disorganization and degeneration in both photoreceptors and the RPE. In the RPE, PKM2 deficiency decreased RPE65 protein levels and impaired the regeneration of 11-cis-retinal, disrupting the visual cycle. PKM2 deletion disrupted the normal cone opsin gradient, indicating that PKM2-dependent metabolic and transcriptional functions are essential for maintaining proper cone organization in the retina. Moreover, rod-specific deletion of PKM2 in Abca4 mutant mice showed early signs of retinal degeneration. The studies described in this manuscript highlight the interdependence of photoreceptor and RPE metabolism and show that PKM2 plays an important role in retinal energy homeostasis and neuronal survival, providing insight into the mechanisms underlying photoreceptor and RPE degeneration in age-related macular degeneration.
    DOI:  https://doi.org/10.1038/s41419-026-08997-3
  6. Biophys Rev. 2026 Apr;18(2): 327-337
    Mitochondrial potassium channels: mitochondria-specific mechanism of regulation.
    Joanna Lewandowska, Barbara Kalenik, Antoni Wrzosek, Bogusz Kulawiak, Piotr Bednarczyk, Barbara Zablocka, Adam Szewczyk.
      Potassium channels identified in the plasma membrane play a crucial role, particularly in generating action potentials in excitable cells. Recently, potassium channels have also been discovered in intracellular organelles, including the inner mitochondrial membrane (IMM), which share many properties with their plasma membrane counterparts. Mitochondrial potassium channels exhibit similar biophysical, pharmacological, and regulatory characteristics, reflecting their common molecular origin. However, differences in potassium channel activity may result from differences in isoforms as well as from the specific ionic, protein, and lipid environments associated with their distinct subcellular locations. In particular, the IMM imposes unique conditions that shape the regulation of mitochondrial potassium channels. These include close proximity to the respiratory chain, high mitochondrial metabolic activity, a pronounced transmembrane potential, and pH gradients. This review examines how these mitochondrial-specific factors influence the function of mitochondrial potassium channels. A deeper understanding of how the IMM environment modulates mitochondrial channel activity will not only expand our knowledge of mitochondrial physiology but may also pave the way for new therapeutic strategies targeting mitochondrial dysfunction and the role of mitochondrial potassium channels in human diseases.
    Keywords:  Kinases; Metabolism; Mitochondria; Mitochondrial potassium channels; Potassium channels openers; Reactive oxygen species; Respiratory chain
    DOI:  https://doi.org/10.1007/s12551-025-01385-9
  7. Front Oncol. 2026 ;16 1784749
    The role of NAD+ metabolic reprogramming in colorectal cancer chemoresistance: mechanistic insights, clinical translation challenges and opportunities.
    Zhennan Ma, Xiuqing Gong, Fuquan Liu.
      As a pivotal hub of cellular metabolism, NAD+ metabolic reprogramming exerts a core role in colorectal cancer chemoresistance by regulating energy metabolism, DNA repair, and the immune microenvironment. The dysregulation of synthetic and catabolic pathways mediated by key molecules such as NAMPT, SIRT1, and PARP constitutes a crucial mechanism underlying chemoresistance development. Targeted intervention strategies against NAD+ metabolism, including precursor supplementation, inhibitor administration, and combination therapy, have exhibited remarkable anti-cancer potential and represent promising translational strategies for reversing chemoresistance. However, clinical translation of these strategies is severely impeded by tumor metabolic heterogeneity, the lack of dynamic NAD+ monitoring technologies and insufficient tissue specificity of targeted drugs. By leveraging emerging techniques including multi-omics integration, organoid models, nano-delivery systems, and dynamic imaging, in-depth dissection of metabolic heterogeneity and development of personalized intervention regimens can provide novel and effective avenues to overcome the predicament of colorectal cancer chemoresistance, which holds important translational research value and clinical application significance.
    Keywords:  NAD+; chemoresistance; colorectal cancer; metabolic reprogramming; targeted intervention
    DOI:  https://doi.org/10.3389/fonc.2026.1784749
  8. mBio. 2026 Jun 15. e0093326
    Arginine metabolism supports de novo pyrimidine biosynthesis to block DNA damage and maintain Epstein-Barr virus latency.
    Shaowen White, Yifei Liao, Yin Wang, Shunji Li, Eric M Burton, John M Asara, Benjamin E Gewurz.
      Incompletely understood mechanisms serve to maintain Epstein-Barr virus (EBV) latency, in which viral oncogene(s) are expressed, but lytic antigens are not expressed. Shortly after the discovery of EBV and even before it was named, Werne and Gertrude Henle identified that restriction of extracellular arginine induces EBV lytic antigens within Burkitt lymphoma tumor cells. However, for nearly 60 years, it has remained unknown how arginine metabolism supports EBV latency. To gain insights, we performed an amino acid restriction screen in EBV+ Burkitt cell lines. This confirmed that arginine restriction was sufficient to trigger EBV reactivation in Burkitt B cells and in gastric carcinoma models. Arginine restriction strongly impaired de novo pyrimidine biosynthesis, and CRISPR- or chemical genetic-blockade of pyrimidine biosynthesis enzymes induced EBV immediate-early and early lytic gene expression. However, arginine restriction blocked EBV lytic DNA replication and, consequently, also late gene expression, suggesting an abortive lytic cycle. By contrast, chemical or CRISPR blockade of the de novo pyrimidine biosynthesis pathway rate-limiting enzyme CAD reactivated a full EBV lytic cycle, suggesting specific arginine restriction roles in support of lytic DNA replication. Arginine restriction caused DNA damage, which was a driver of EBV reactivation. Arginine restriction and DNA hypomethylation additively reactivated EBV. Together, our results highlight arginine and pyrimidine metabolism as potential targets for EBV lytic antigen induction therapy in B-cell and epithelial-cell contexts.
    IMPORTANCE: Altered metabolism is a hallmark of cancer, frequently increasing transformed cell dependence on extracellular amino acid supply. Despite current interest in Epstein-Barr virus (EBV) lytic antigen induction therapy, in which viral lytic reactivation sensitizes tumors to the highly cytotoxic effects of the antiviral ganciclovir, there has been no systematic study of extracellular amino acids that control EBV latency. We identified that arginine uptake was important for the maintenance of EBV latency in both Burkitt lymphoma and gastric carcinoma contexts. Metabolic pathway analyses highlighted that arginine uptake and metabolism were required to supply pyrimidines. Disruption of arginine metabolism or de novo pyrimidine synthesis caused DNA damage. Arginine restriction also triggered Burkitt DNA hypermethylation. Building upon this, we provide evidence that the combination of arginine restriction and DNA hypomethylation, either by decitabine or by CRISPR approaches, induced EBV reactivation more strongly than either alone, suggesting a therapeutic approach..
    Keywords:  DNA damage; de novo pyrimidine synthesis; double-stranded DNA virus; epigenetic; lytic cycle; metabolism; nucleotide biosynthesis; nucleotide metabolism; reactivation; viral latency
    DOI:  https://doi.org/10.1128/mbio.00933-26
  9. Sci Rep. 2026 Jun 17. pii: 18698. [Epub ahead of print]16(1):
    Messenger RNA-encoded reporters for monitoring cellular stress and bioenergetics.
    Karen Kai-Lin Hwang, Qi Fang, Carine Nizard, Anne-Laure Bulteau, Knut Woltjen.
      The ability to monitor cellular processes in real-time is essential for understanding cell function, disease progression, and therapeutic responses. Engineered reporter proteins have been developed for monitoring cellular metabolism, stress responses, and bioenergetics. However, their use in primary cells is limited by inefficient plasmid transfection and the impracticality of generating and validating stable cell lines for each application. Here, we use in vitro transcription to generate mRNA-encoded metabolic trackers and achieve high transfection efficiencies in primary fibroblasts, cancer cells, and induced pluripotent stem cells. This approach provides a flexible platform for real-time monitoring of cellular processes in diverse cell types and overcomes the technical barriers of establishing stable cell lines by genetic modification. We confirm the activity of three ratiometric reporters that monitor pH, H2O2, and ATP levels in subcellular compartments. Our mRNA-based approach provides a versatile, efficient tool for real-time metabolic studies across basic and applied research, reducing reliance on commercially available reporters and broadening the applicability of metabolic reporters in patient-derived cell models.
    Keywords:  ATP; Bioenergetics; Messenger RNA; Metabolic reporters; Reactive oxygen species; pH
    DOI:  https://doi.org/10.1038/s41598-026-49851-y
  10. J Clin Invest. 2026 06 15. pii: e173913. [Epub ahead of print]136(12):
    Pancreatic islet α cell function and proliferation require the arginine transporter SLC7A2.
    Erick Spears, Jade E Stanley, Matthew Shou, Linlin Yin, Xuan Li, Chunhua Dai, Amber Bradley, Katelyn Sellick, Greg Poffenberger, Katie C Coate, Shristi Shrestha, Anna Marie R Schornack, Taverlyn Shepard, Madushika Wimalarathne, Regina Jenkins, Kyle W Sloop, Keith T Wilson, Alan D Attie, Mark P Keller, Wenbiao Chen, Alvin C Powers, E Danielle Dean.
      Interrupting glucagon signaling decreases gluconeogenesis and the fractional extraction of amino acids by liver from blood, resulting in lower glycemia. The resulting hyperaminoacidemia stimulates α cell proliferation and glucagon secretion via a liver/α cell axis. We hypothesized that α cells detect and respond to circulating amino acids' levels via a unique amino acid transporter repertoire. We found that Slc7a2/SLC7A2 is the most highly expressed cationic amino acid transporter in α cells, with its expression being 3-fold greater in α than β cells in both mouse and human. Employing cell culture, zebrafish, and knockout mouse models, we found that the cationic amino acid arginine and SLC7A2 are required for α cell proliferation in response to interrupted glucagon signaling. Ex vivo and in vivo assessment of islet function in Slc7a2-/- mice showed decreased arginine-stimulated glucagon and insulin secretion. We found that arginine activation of mTOR signaling and induction of the glutamine transporter SLC38A5 was dependent on SLC7A2, showing that the role of both in α cell proliferation is dependent on arginine transport and SLC7A2. Finally, we identified single nucleotide polymorphisms in SLC7A2 associated with HbA1c. Together, these data indicate a central role for SLC7A2 in amino acid-stimulated α cell proliferation and islet hormone secretion.
    Keywords:  Amino acid metabolism; Cell biology; Endocrinology; Insulin; Islet cells; Metabolism
    DOI:  https://doi.org/10.1172/JCI173913
  11. Nat Cell Biol. 2026 Jun 19.
    Lysosome-derived methylated arginine is a signalling metabolite controlling the lipidome.
    Steven T Nguyen, Richard L Watson, Fangyuan Gao, Melissa Campos, Sunhee Jung, Laurence J Seabrook, Maxwell C Kim, Eric A Hanse, Ying Yang, Mei Kong, Jonathan E Zuckerman, Renata C Pereira, Isidro B Salusky, Sergio D Catz, Cholsoon Jang, Dorota Skowronska-Krawczyk, Lauren V Albrecht.
      Lysosomes are integral organelles that communicate cellular status to an entire tissue through mechanisms that are poorly defined. Here we developed an unbiased platform, integrating human plasma metabolomes and single-lysosome metabolomics, and show the byproducts of proteolysis are an unexpected class of signalling molecules. We show that dimethylarginine is a lysosomal-derived metabolite and a predictor of patient morbidity. Genetic depletion of a lysosomal exporter, cystinosin, accumulated dimethylarginine in lysosomes. Leveraging a lysosomal storage disease with cystinosin mutations, we show that the rapid plasticity of dimethylarginine compartmentalization ensures cell and tissue homeostasis. Strikingly, lysosomal entrapment of dimethylarginine in patients and disease models corresponds with lipid accumulation, lipid droplets and lipotoxicity. Exogenously restoring asymmetric dimethylarginine buffers oxidative stress, decreasing lipid peroxidation and cell death. These data show that dimethylarginine engages an interorganellar process-with peroxisomes, lysosomes and lipid droplets-that confers a crucial adaptive response mechanism.
    DOI:  https://doi.org/10.1038/s41556-026-01970-4
  12. Curr Opin Chem Biol. 2026 Jun 17. pii: S1367-5931(26)00056-6. [Epub ahead of print]93 102707
    Chemigenetic fluorescent biosensors in biological imaging - New trends and advances.
    Dennis Pellanda, Elias Dressler, Michelle S Frei.
      Chemigenetic fluorescent biosensors combine genetically encoded and synthetic approaches, showing superior photophysical properties compared with fluorescent protein-based tools and enabling subcellular and tissue specific targeting as well as selective analyte detection. Here, we review how two of the most widely used chemigenetic systems, HaloTag and fluorescence-activating and absorption-shifting tag (FAST), have been incorporated into biosensors and used to expand the functionality of biosensors. We highlight how bright, photostable, and far-red fluorophores improve in vivo and multiplexed imaging. We discuss how chemigenetic biosensors with fluorescence lifetime readouts are advancing quantitative imaging through fluorescence lifetime imaging microscopy (FLIM) and we showcase chemigenetic integrators that can record physiological events for post hoc analysis. Finally, we offer an outlook on where chemigenetic biosensors are headed and their anticipated impact on biological imaging in the coming years.
    DOI:  https://doi.org/10.1016/j.cbpa.2026.102707
  13. PLoS Biol. 2026 Jun 15. 24(6): e3003856
    Aging and metabolism contribute separately to brain-body health.
    Asa Farahani, Zhen-Qi Liu, Filip Morys, Roqaie Moqadam, Yashar Zeighami, Mahsa Dadar, Alain Dagher, Bratislav Misic.
      The brain and body undergo coordinated changes throughout the life span, yet studies of aging have traditionally examined these systems as separate entities. Here we ask how brain health relates to aging and peripheral biomarkers of metabolic and vascular function, including body mass index, blood pressure, and blood biochemistry. We use multivariate pattern learning to identify generalizable patterns of covariance between multi-modal neuroimaging data (structural, functional, diffusion, and arterial spin labeling MRI), demographic, and physiological markers in two large-scale deeply phenotyped datasets: the Human Connectome Project-Aging and UK Biobank. This data-driven approach isolates two principal axes of brain-body associations in both biological sexes. The first axis is driven by the dominant contribution of age. Across multiple brain measures, aging is associated with loss of brain structural integrity and cerebral vascular dysfunction. The second axis is driven by metabolic features, characterized by low high-density lipoprotein cholesterol, elevated body mass index, blood pressure, glycosylated hemoglobin, insulin, glucose, and alanine aminotransferase that predominantly converge on reduced cerebral perfusion. Importantly, the aging and the metabolic axes are independent of each other, meaning that age and metabolic dysfunction have separable influences on the brain. Finally, we show that deviations from a healthy metabolic profile are linked to cognitive deficits, particularly in females. Our study contributes to development of comprehensive translatable biomarkers for brain health assessment, and highlights the importance of metabolic health as a determinant of brain health in aging population.
    DOI:  https://doi.org/10.1371/journal.pbio.3003856
  14. Nat Struct Mol Biol. 2026 Jun;33(6): 1011-1019
    A single-vesicle fluorescence microscopy platform to quantify phospholipid scrambling.
    Sarina Veit, Grace I Dearden, Kartikeya M Menon, Faria Noor, Indu Menon, Takefumi Morizumi, Oliver P Ernst, Anant K Menon, Thomas Günther Pomorski.
      Scramblases are physiologically important proteins that translocate phospholipids bidirectionally across cell membranes. For example, scrambling facilitated by dimers of the voltage-dependent anion channel 1 (VDAC1) enables endoplasmic reticulum-derived phospholipids to cross the outer membrane to enter mitochondria. Here we describe a protocol to obtain lipid translocation rates at a single-protein level, allowing for mechanistic understanding of scramblases. We reconstituted vesicles with fluorescent phospholipids and VDAC1 dimers and use high-throughput imaging to quantify their size and dimer content. We measure scrambling in each vesicle using a new assay and find that individual human VDAC1 dimers scramble lipids at rates ranging from under 100 to over 10,000 per second. This kinetic heterogeneity, masked in ensemble measurements, revealed that rapid scrambling is facilitated by specific VDAC1 dimers. Extending our analyses to bovine opsin, a monomeric G-protein-coupled receptor scramblase, we demonstrate the versatility of our platform for quantifying lipid scrambling and exploring its regulation.
    DOI:  https://doi.org/10.1038/s41594-026-01821-8
  15. Neuron. 2026 Jun 16. pii: S0896-6273(26)00371-5. [Epub ahead of print]
    Mitochondria and brain aging: From cell-specific dysfunction to intercellular cooperation.
    Amandine Grimm, Undine Lang, Anne Eckert.
      Mitochondria are essential for brain energy metabolism and are increasingly recognized as key contributors to brain aging. Although neurons are exceptionally vulnerable to age-related mitochondrial decline, emerging evidence reveals that glial and vascular cells also exhibit distinct mitochondrial impairments. This review synthesizes recent advances in our understanding of mitochondrial dysfunction across specific brain regions and diverse cell types, highlighting subcellular compartmentalization and metabolic rewiring. We further explore intercellular mitochondrial transfer as a novel form of metabolic cooperation, as well as the therapeutic potential of mitochondrial transplantation. Finally, we highlight recent clinical trials evaluating mitochondria-targeted interventions aimed at preserving brain function in older adults. Together, these findings reposition mitochondria as both integrators and amplifiers of brain aging processes across diverse cell populations. By broadening the focus beyond neurons and emphasizing translational efforts, we offer a comprehensive framework for understanding and therapeutically targeting mitochondrial dysfunction in age-related cognitive decline and neurodegeneration.
    Keywords:  aging; astrocytes; blood-brain barrier; brain; intercellular mitochondrial transfer; microglia; mitochondria; mitochondrial transplantation; neurons; oligodendrocytes
    DOI:  https://doi.org/10.1016/j.neuron.2026.04.048
  16. Nucleic Acids Res. 2026 Jun 17. pii: gkag384. [Epub ahead of print]
    LiMeNEx: an interactive webserver on lipid biochemical gene-regulatory network.
    Diksha Marwaha, Aishwary Sharma, Kartikeya Saini, Aryan K Singh, Akash Bhaskar, Arjun Ray.
      Lipid metabolism represents an intricate landscape of biochemical reactions catalyzed by enzymes and regulated by transcription factors (TFs) to maintain metabolic homeostasis. Disruption of the enzymatic or transcriptional machinery is associated with lipid imbalance, contributing to diverse pathological conditions across tissues and the physiological system. However, existing pathway resources predominantly focus on metabolic map reactions but lack integration of upstream regulatory components, limiting system-level interrogation of lipid-associated mechanisms. We present LiMeNEx (Lipid Metabolic Network Explorer), an interactive webserver for exploration of lipid biochemical gene regulatory networks that link lipids, enzymes, and TFs. LiMeNEx integrates carefully curated 504 biochemical reactions across 22 lipid pathways, involving 330 enzymatic genes and 345 TFs mapped across 50 human tissues and 11 physiological systems. The three consols of LiMeNEx allow users to query lipids for visualization of lipid pathways and genes involved in lipid-enzyme reactions, and to explore tissue and systems-specific transcriptional regulators of target genes. LiMeNEx provides a holistic view of lipid metabolism with comprehensive documentation for intuitive navigation. By integrating metabolic and regulatory layers in a tissue-resolved framework, it enables hypothesis-driven system-level investigation of lipid metabolism and related disorders. LiMeNEx is freely available at https://limenex.raylab.iiitd.edu.in/.
    DOI:  https://doi.org/10.1093/nar/gkag384
  17. Front Immunol. 2026 ;17 1850399
    Glycolytic reprogramming in ovarian cancer: mechanisms, immune crosstalk, and therapeutic implications.
    Jiao Fu, Yi Dai, Qiaoling Wang, Xiayu Qian.
      Ovarian cancer is characterized by extensive peritoneal dissemination, frequent recurrence, and chemoresistance. Glycolytic reprogramming has emerged as a central metabolic adaptation in ovarian cancer, but its significance extends beyond increased glucose consumption. In this review, we summarize how key glycolytic regulators, including GLUT1, HK2, PFKFB3, PDK1, and LDHA, are controlled by oncogenic, microenvironmental, and non-coding RNA-mediated pathways to reshape tumor metabolism. We emphasize that glycolysis supports ovarian cancer progression by promoting biosynthetic activity, redox balance, invasive dissemination, stem-like plasticity, and therapy resistance. Importantly, this review highlights glycolysis as an immunometabolic regulator of the ovarian tumor microenvironment. Lactate accumulation, macrophage reprogramming, IL-1β/NF-κB signaling, PD-L1 induction, and CD4+ T-cell metabolic remodeling collectively contribute to immune escape. Targeting glycolytic pathways may therefore provide therapeutic opportunities not only to suppress tumor growth but also to enhance chemotherapy and immunotherapy. However, metabolic heterogeneity, compensatory pathway activation, limited biomarkers, and insufficient clinical validation remain major challenges. A glycolysis-centered understanding of ovarian cancer may support biomarker-guided combination strategies and improve translational therapeutic design.
    Keywords:  chemoresistance; glycolysis; immune crosstalk; metabolic reprogramming; ovarian cancer
    DOI:  https://doi.org/10.3389/fimmu.2026.1850399
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