bims-nimamd Biomed News
on Neuroimmunity and neuroinflammation in ageing and metabolic disease
Issue of 2026–10–18
twenty-one papers selected by
Fawaz Alzaïd, Sorbonne Université
  1. Unprecedented atlas explores mitochondria across the tree of life.
  2. Systemic proteomic dynamics of acute exercise reveal genetic links to health and disease.
  3. A multi-fluid exercise proteomic atlas reveals regulators of health and disease.
  4. Directionality of transcriptional regulatory elements.
  5. Astrocytes go into presenter mode.
  6. An aging-sensitive secreted phospholipase confers neuroprotection and cognitive resilience.
  7. Whistleblowing in universities is 'extraordinarily risky': stronger protections are needed.
  8. Mitochondria strike two hits to drive the SASP.
  9. Overlooked brown fat in our bodies linked to wide range of health benefits.
  10. Give me the good news: four science stories to brighten your day.
  11. A neural circuit of food sight-promoted feeding and contextual memory in mice.
  12. Insulin sensitivity and mitochondrial homeostasis connect lactation to maternal metabolic health.
  13. Endothelial cell-microglia crosstalk mediates heart failure-associated synaptic loss and cognitive impairment in male mice.
  14. IRF7 signalling in tanycytes controls brain-body-immune response across the ovarian cycle.
  15. Lipid droplet-induced T cell death sustains autoimmune tissue inflammation.
  16. Resolving the links between efferocytosis and DNMT3A mutation-driven clonal hematopoiesis in atherosclerosis.
  17. Genome-wide CRISPR screen reveals that Wnt signaling regulates lipid accumulation in APOE4 oligodendrocytes.
  18. High-Fat Diet-Induced Metabolic Stress Durably Reprograms the Liver Regenerative Compartment Toward a Senescence-Like State.
  19. Himito: a graph-based toolkit for mitochondrial genome analysis using long reads.
  20. FDA Approves a Second Weekly Basal Insulin Option for Type 2 Diabetes.
  21. ATAD-3 couples plasma membrane injury to mitochondrial Ca2+ signaling.
  1. Nature. 2026 Oct 16.
    Unprecedented atlas explores mitochondria across the tree of life.
    Miryam Naddaf.
      
    Keywords:  Cell biology; Drug discovery
    DOI:  https://doi.org/10.1038/d41586-026-03195-9
  2. Nat Metab. 2026 Oct 12.
    Systemic proteomic dynamics of acute exercise reveal genetic links to health and disease.
    Nigel Kurgan, Jeppe Kjærgaard, Naja Zenius Jespersen, Virginia Díez-Obrero, Victor Svenstrup, Roger Moreno-Justicia, Sarah Elizabeth Heywood, Cecilie Bergmann Lindqvist, Lisa Ottander, Diana Samodova-Sommer, Alina Malita, Olga Kubrak, Nadja Ahrentløv, Nina Sloth Nielsen, Cody Garett Durrer, Michael Texada, Mathias Ried-Larsen, Simon Rasmussen, Kim Rewitz, Ruth J F Loos, Roelof Adriaan Johan Smit, Bente Klarlund Pedersen, Atul Shahaji Deshmukh.
      Physical activity improves metabolic health, but the molecular responses that mediate its benefits are not fully characterized. Here we present a high-resolution, time-resolved proteomics atlas across plasma, saliva and urine from 25 healthy men in response to acute exercise. We find that exercise regulates more than 3,000 proteins through distinct, fluid-specific temporal dynamics. Network analysis uncovers coordinated remodelling of protein secretion, extracellular matrix and immune activation across body fluids. Replication in an independent cohort shows that many exercise-responsive plasma proteins exhibit consistent responses across age, sex and exercise modalities. Integration with human genome-wide association study data links secreted, exercise-responsive proteins to cardiometabolic diseases. Functional validation of genetically prioritized muscle-specific secreted proteins in Drosophila confirms their role in endurance, behaviour and metabolism. Overall, this open-access atlas ( https://cbmr.ku.dk/research/research-groups/deshmukh-group/shiny-apps/ ) provides a multifluid resource that complements existing exercise-omics efforts for defining molecular adaptations to exercise and for prioritizing candidate exerkines.
    DOI:  https://doi.org/10.1038/s42255-026-01621-w
  3. Nat Metab. 2026 Oct 12.
    A multi-fluid exercise proteomic atlas reveals regulators of health and disease.
      
    DOI:  https://doi.org/10.1038/s42255-026-01642-5
  4. Nat Commun. 2026 09 10. pii: 10671. [Epub ahead of print]17(1):
    Directionality of transcriptional regulatory elements.
    You Chen, Sagar R Shah, Alden K Leung, Mauricio I Paramo, Caralyn Gonzales, Kelly Cochran, Austin Wang, Anshul Kundaje, Andrew G Clark, John T Lis, Haiyuan Yu.
      Divergent transcription is a critical marker of active transcriptional regulatory elements (TREs), including enhancers and promoters, in mammals. However, distal elements with unidirectional transcriptional patterns are often overlooked, leaving their identity and function poorly understood. Here, we perform a systematic comparison between divergent and unidirectional elements, revealing their distinct architectural and functional features. Our analysis also shows that unidirectional elements have younger sequence ages and are under weaker evolutionary constraints than divergent elements, suggesting that they may represent a unique category of genomic regulatory function with more recent origins. Furthermore, we investigate factors involved in transcriptional directionality at TREs, with CTCF and ZNF143 showing dual, position-dependent roles in transcriptional modulation. Overall, the elucidation of directionality enhances our understanding of the diverse architectural models, functional features, evolutionary dynamics, and regulatory logic of TREs.
    DOI:  https://doi.org/10.1038/s41467-026-76415-5
  5. Immunity. 2026 Oct 13. pii: S1074-7613(26)00389-4. [Epub ahead of print]59(10): 2620-2622
    Astrocytes go into presenter mode.
    Lara Labarta-Bajo, Nicola J Allen.
      Astrocytes are glial cells important for neuronal health, but their functions in CNS immunopathology are less understood. In a recent issue of Nature, Lee et al. report that CD40 engagement and proinflammatory cytokines promote lipid droplet accumulation in astrocytes and subsequent antigen presentation, boosting pathogenic CD4+ T cell responses during experimental autoimmune encephalomyelitis.
    DOI:  https://doi.org/10.1016/j.immuni.2026.09.014
  6. Nat Neurosci. 2026 Oct 15.
    An aging-sensitive secreted phospholipase confers neuroprotection and cognitive resilience.
    Cinzia Vicidomini, Travis D Goode, Ruilin Yu, Iyanah Mehta, Kathleen M McAvoy, Connor H Beveridge, Caitlin E Randolph, Sanjay N Iyer, Matheus B Victor, Noelle Leary, Liam Evans, Michael J Steinbaugh, Zon Weng Lai, Marina C Lyon, Manuel Rico Fernández San Silvestre, Giorgia Tosoni, Dilara Ayyildiz, Shannan Ho Sui, Kei Yamamoto, Makoto Murakami, Evgenia Salta, Li-Huei Tsai, Gaurav Chopra, Amar Sahay.
      Cognitive reserve theory posits that compensatory mechanisms during aging stave off cognitive decline and lower risk for Alzheimer's disease. Here, in a screen for hippocampal dentate granule cell (DGC) synapse loss-induced factors in mice, we identified a secreted phospholipase, Pla2g2f, whose expression increases in DGCs during aging and is associated with cognitive resilience in humans. Pla2g2f deletion in DGCs exacerbates aging-associated pathophysiological changes, including synapse loss, inflammatory microglia, reactive astrogliosis, impaired neurogenesis, lipid dysregulation, lipid droplet accumulation and hippocampal-dependent memory loss. Conversely, boosting Pla2g2f in DGCs during aging is sufficient to prevent these pathophysiological alterations in hippocampal-cortical circuits, protect memory and prophylactically modify trajectory of cognitive decline. Mutagenesis of the catalytic site of PLA2G2F prevented lipid droplet mobilization and reduction of reactive gliosis and inflammatory microglia. Neuronal PLA2G2F mediates intercellular signaling to decrease lipid droplet and cholesterol ester load in human induced pluripotent stem cell-derived microglia. Our findings implicate PLA2G2F as a compensatory neuroprotective broadcast signal that maintains lipid homeostasis to counteract aging-associated cognitive decline.
    DOI:  https://doi.org/10.1038/s41593-026-02465-z
  7. Nature. 2026 Oct;658(8136): 582
    Whistleblowing in universities is 'extraordinarily risky': stronger protections are needed.
    N Wyn Evans.
      
    Keywords:  Ethics; Policy; Scientific community
    DOI:  https://doi.org/10.1038/d41586-026-03221-w
  8. Dev Cell. 2026 Oct 14. pii: S1534-5807(26)00358-8. [Epub ahead of print]61(10): 1945-1946
    Mitochondria strike two hits to drive the SASP.
    Jun Bum Park, Zhixun Dou.
      Senescent cells develop a persistent inflammatory signature with broad consequences for tissue function and disease. Martini et al.1 show that mitochondrial citrate metabolism drives inflammation through a pathway that acts independently of mitochondrial DNA-driven immune signaling yet cooperates with it to amplify the inflammatory response.
    DOI:  https://doi.org/10.1016/j.devcel.2026.09.010
  9. Nature. 2026 Oct 14.
    Overlooked brown fat in our bodies linked to wide range of health benefits.
    Mariana Lenharo.
      
    Keywords:  Computer science; Diseases; Metabolism
    DOI:  https://doi.org/10.1038/d41586-026-03302-w
  10. Nature. 2026 Oct 15.
    Give me the good news: four science stories to brighten your day.
    Rachel Fieldhouse.
      
    Keywords:  Diabetes; Medical research; Ocean sciences
    DOI:  https://doi.org/10.1038/d41586-026-03152-6
  11. Nat Commun. 2026 09 11. pii: 10719. [Epub ahead of print]17(1):
    A neural circuit of food sight-promoted feeding and contextual memory in mice.
    Juemou Zhou, Fumiao Zhang, Chen-Ma Wang, Ting Ouyang, Mingming Xing, Xiaoli Cui, Danting Ma, Chunguang Liu, Xiaofeng Shi, Bojie Hu, Shuli Zhang, Yuqi Zhang, Weiping J Zhang, Xiangyang Xie.
      Feeding is regulated not solely by intrinsic energy demands, but also by various environmental cues. Food sight and odor are two essential food-related cues that promote human eating; nonetheless, the underlying neural mechanisms remain unknown. Here, we show that during energy deficit, food sight inhibits the ventromedial hypothalamus (VMH) neuronal activity, thereby promoting feeding and food-associated contextual memory in mice. VMH neurons receive direct GABAergic input from the suprachiasmatic nucleus (SCN) that is rapidly activated by food sight. Either knockout of VMH RuvB-like 2 (RUVBL2) or inhibition of RUVBL2-expressing neurons in the VMH (VMHRUVBL2) promotes feeding and food-associated contextual memory. Interestingly, VMHRUVBL2 neurons exert these effects by sequentially projecting to the supramammillary nucleus (SuM) and the hippocampal dentate gyrus (DG). Together, this study identifies SCNGABA → VMHRUVBL2 → SuM→DG neural circuit underlying food sight-promoted feeding and food-associated contextual memory in mice.
    DOI:  https://doi.org/10.1038/s41467-026-77682-y
  12. J Clin Invest. 2026 Oct 15. pii: e210439. [Epub ahead of print]136(20):
    Insulin sensitivity and mitochondrial homeostasis connect lactation to maternal metabolic health.
    Laura L Hernandez.
      Lactation insufficiency in postpartum women has been associated with obesity and insulin resistance, among other risk factors. Challenges related to translating findings from animal models of lactation and the limited ability to study pregnant and lactating women in clinical trials have impeded more detailed mechanistic understanding of this relationship. In this issue of the JCI, Meng et al. combined studies in human milk samples and in vitro mammary epithelial cell models from humans and rodents to provide compelling evidence that mitochondrial dysfunction mediates the link between insulin resistance and lactation insufficiency. Notably, they observed that chronic exposure to high levels of insulin led to mitochondrial fragmentation and loss of volume in mouse mammary epithelial cells. This framework linking mitochondria, insulin signaling, and lactation should be extended to in vivo models and primary human tissues to better define the mechanisms supporting successful lactation.
    DOI:  https://doi.org/10.1172/JCI210439
  13. Nat Commun. 2026 08 14. pii: 10722. [Epub ahead of print]17(1):
    Endothelial cell-microglia crosstalk mediates heart failure-associated synaptic loss and cognitive impairment in male mice.
    Mengdan Wang, Xiaoxuan Yu, Tursunjan Aziz, Shiyao Zhang, Xiao Wu, Weiyin Wu, Yan Wang, Gang Li, Shuo Zhang.
      Cognitive impairment affects 30%-80% of patients with heart failure, yet the mechanisms beyond reduced brain blood flow remain poorly defined. Here we show that circulating factors released during heart failure trigger senescence of brain blood-vessel endothelial cells, which in turn drives synaptic loss and cognitive decline through crosstalk between endothelial cells and microglia, the brain's immune cells. Using a pressure-overload model (transverse aortic constriction) combined with plasma transfer in 8-month-old male mice, we found that elevated circulating TGFβ2 acts on endothelial TGFBR2 and induces the secreted protein SPARC via a non-canonical MEK/ERK-MYC pathway. Endothelial SPARC then activates microglial TLR4, promoting neuroinflammation and abnormal engulfment of synapses. Endothelial deletion of Tgfbr2 or Sparc, and microglial deletion of Tlr4, each preserved synapses and improved cognition, and pharmacological Tlr4 inhibition was protective. These findings define an endothelial-microglia signaling axis and a potential therapeutic target in heart failure-associated cognitive impairment.
    DOI:  https://doi.org/10.1038/s41467-026-76687-x
  14. Nat Metab. 2026 Oct 15.
    IRF7 signalling in tanycytes controls brain-body-immune response across the ovarian cycle.
    Sreekala Nampoothiri, Daniela Fernandois, Nathalie Journiac, Fabien Delahaye, Yvon Mbouamboua, Florent Sauve, Marie Couralet, Sarah Gallet, Naziha Mroueh, Maria Laura Serradas Aponte, Nathalie Jouy, Rachel Spenle, Ruth Schmidt-Ullrich, Ines Martinez Corral, Virginie Mattot, Carmen Ruiz de Almodovar, Andreas Schlitzer, Philippe Froguel, Claude-Alain Maurage, Pascal Barbry, Paolo Giacobini, Lennart T Mars, Amelie Bonnefond, Ruben Nogueiras, Markus Schwaninger, Vincent Prevot.
      Sex-specific differences in metabolic and immune function are shaped by endocrine-immune interactions, yet the complexity of this relationship remains poorly understood. Here, we identify an immune cell-like state of tanycytes, an ependymoglial cell type lining the third ventricle that mediates brain-body communication1,2 in both mice and humans. Using single-cell transcriptomics, we provide a high-resolution cellular map of the mouse and human mediobasal hypothalamus with cross-species comparison of tanycytes. We capture dynamic sex-, oestrous cycle- and high-fat diet-dependent transcriptomic changes in tanycytes, including a cyclic interferon response in tanycytes during the physiological oestrous cycle in female mice. We found that the oestrous cycle, with its changing hormonal milieu, especially oestradiol, affected the brain's immune responses, characterized by the temporal and cyclic expression of interferon regulatory factor 7 (Irf7) gene, as well as downstream interferon-stimulated genes such as Cxcl10 in tanycytes of female mice, which are associated with increased infiltration of leukocytes and cytokine responses. Irf7 expression in tanycytes of physiological males remained stable and markedly lower, suggesting a distinct immune activation pattern in the brains of cycling females. By targeting oestrogen and interferon signaling in tanycytes, we show that balanced, cyclic leukocyte infiltration into the median eminence may have a role in oestrous cycle maintenance, whereas Irf7 in tanycytes modulates circulating monocyte proportions, revealing brain-immune system communication through tanycytes. Our findings reveal an immune-associated role for tanycytes, with potential implications for understanding the endocrine and immunological mechanisms underlying sex-biased diseases.
    DOI:  https://doi.org/10.1038/s42255-026-01635-4
  15. Cell Metab. 2026 Oct 09. pii: S1550-4131(26)00440-7. [Epub ahead of print]
    Lipid droplet-induced T cell death sustains autoimmune tissue inflammation.
    Jitendra Kumar, Yoshinori Takashima, Jose Morales, Brandon Wong, Lina Werner, Isabel N Goronzy, Selene Rubino, Robert T Trousdale, Gerald J Berry, Jörg J Goronzy, Cornelia M Weyand.
      
    DOI:  https://doi.org/10.1016/j.cmet.2026.10.003
  16. J Clin Invest. 2026 Oct 15. pii: e211265. [Epub ahead of print]136(20):
    Resolving the links between efferocytosis and DNMT3A mutation-driven clonal hematopoiesis in atherosclerosis.
    Aarti Asnani.
      Efferocytosis, or the clearance of apoptotic cells by macrophages, has been implicated in tissue resolution that promotes disease regression in atherosclerosis and other diseases of chronic inflammation. The mechanisms by which efferocytosis leads to pro-resolving macrophage reprogramming have not been fully defined. In this issue of the JCI, Avrampou and colleagues found that efferocytosis activates DNA-methyltransferase-3A (DNMT3A) to promote base excision repair and suppress oxidized DNA. Moreover, they provide evidence that DNMT3A enabled tissue repair in the context of plaque regression in a mouse model of atherosclerosis. Human studies have linked DNMT3A mutation-mediated clonal hematopoiesis (DNMT3A-CH) with atherosclerosis. The findings of Avrampou et al. linking DNMT3A function to efferocytosis-mediated tissue repair suggest that this pathway could be modulated therapeutically to minimize cardiovascular events in patients.
    DOI:  https://doi.org/10.1172/JCI211265
  17. Cell Stem Cell. 2026 Oct 15. pii: S1934-5909(26)00354-1. [Epub ahead of print]
    Genome-wide CRISPR screen reveals that Wnt signaling regulates lipid accumulation in APOE4 oligodendrocytes.
    Leyla Anne Akay, Anna Bright, Daiyun Dong, Ethan D Smith, Robert C Hurt, Carles A Boix, Kate Louderback, Janine Medrano, Dingcheng Sun, Haonan Lin, Oisín King, Gwyneth M Welch, Hiba Nawaid, Emre Agbas, Alan Jiang, Adele Bubnys, Ji-Xin Cheng, Joel W Blanchard, Li-Huei Tsai.
      APOE4 is the strongest genetic risk factor for late-onset Alzheimer's disease, yet the cellular mechanisms linking APOE variants to disease risk remain unclear. We previously found that APOE4 expression causes lipid droplet accumulation in oligodendrocytes, reducing myelination, but the underlying mechanisms were unknown. Using a genome-wide CRISPR screen and assay for transposase-accessible chromatin (ATAC) sequencing in human-induced pluripotent stem cell (iPSC)-derived oligodendrocytes, we identified decreased Wnt signaling and overactive glycogen synthase kinase-3 beta (GSK3B) as key regulators of lipid-droplet accumulation. Genetic and pharmacological inhibition of GSK3B reduced lipid droplets in APOE4 oligodendrocytes and increased myelination in three-dimensional iPSC-derived brain organoids. Pharmacological GSK3B inhibition also reduced lipid droplets and improved myelination in APOE4;PS19 tau transgenic mice. Together, these findings establish a mechanistic framework linking Wnt/GSK3B signaling to APOE4-driven disruptions in oligodendrocyte lipid metabolism and myelination, pointing to GSK3B as a potential therapeutic target for APOE4-associated Alzheimer's disease.
    Keywords:  APOE; Alzheimer’s disease; GSK3B; WNT signaling; lipid droplet accumulation; myelination
    DOI:  https://doi.org/10.1016/j.stem.2026.09.012
  18. Aging Cell. 2026 Oct;25(10): e70769
    High-Fat Diet-Induced Metabolic Stress Durably Reprograms the Liver Regenerative Compartment Toward a Senescence-Like State.
    Mirai Yamazaki, Hiroya Yamada, Eiji Munetsuna, Yoshitaka Ando, Genki Mizuno, Takuya Wakasugi, Tomohide Sakakibara, Kumpei Hada, Hayato Ichikawa, Ryoga Senga, Moeno Asai, Hiroaki Ishikawa, Koji Suzuki, Koji Ohashi, Nobutaka Ohgami.
      Chronic metabolic stress is increasingly recognized as a driver of aging-like tissue dysfunction, but whether it durably reprograms liver regenerative cells, potentially compromising tissue maintenance and repair, remains unknown. Here, we show that high-fat diet (HFD)-induced metabolic stress promotes a persistent senescence-like state in the liver regenerative compartment. In male rats, chronic HFD feeding induced hepatic steatosis together with oxidative stress, inflammatory responses, and senescence-associated changes. Following carbon tetrachloride-induced liver injury, HFD-fed animals exhibited reduced proliferative responses. To determine whether these abnormalities were durably retained within regenerative cell populations, we established liver organoids from control and HFD-fed rats. HF-derived organoids showed reduced formation efficiency and impaired serial propagation capacity outside the original metabolic environment. Senescence-associated abnormalities, including increased senescence-associated β-galactosidase staining, reduced Lamin B1 staining, and decreased Ki67 positivity, remained detectable through Passage 3. Transcriptomic and functional analyses revealed mitochondrial dysfunction and enhanced oxidative and inflammatory responses. These organoids also exhibited enhanced lipid accumulation and inflammatory secretion following fatty acid challenge. Treatment with the mitochondria-targeted antioxidant MitoQ reduced oxidative stress and inflammatory secretion, improved oxygen consumption, and partially restored organoid formation efficiency, supporting a functional contribution of mitochondrial dysfunction to regenerative impairment. Together, these findings support a model in which chronic metabolic stress leaves persistent senescence-like dysfunction within the liver regenerative compartment, extending its consequences beyond abnormalities in mature liver tissue.
    Keywords:  cellular senescence; liver progenitor; liver regeneration; metabolic dysfunction‐associated steatotic liver disease (MASLD); metabolic stress; mitochondrial dysfunction; organoid; stem cell aging
    DOI:  https://doi.org/10.1111/acel.70769
  19. Nat Commun. 2026 Sep 10. pii: 10668. [Epub ahead of print]17(1):
    Himito: a graph-based toolkit for mitochondrial genome analysis using long reads.
    All of Us Research Program Long Read Working Group
      Understanding the genetic and epigenetic regulation of mitochondrial DNA (mtDNA) is essential for elucidating mechanisms of aging and disease. Long-read sequencing can span the mitochondrial genome and capture base-modification signals, yet analytical tools remain limited. We developed Himito, a graph-based toolkit for analyzing mitochondrial genome using long reads. Himito filters reads originating from nuclear mitochondrial insertions (NUMTs), constructs a sequence graph to represent mtDNA diversity, assembles primary haplotypes, calls variants, and analyzes 5-methylcytosine (5mC) modifications within a unified framework. Benchmarking on reference datasets shows Himito achieves superior performance in assembly and variant calling compared with existing tools. Applied to the All of Us (AoU) v8 dataset, Himito identified pathogenic mtDNA variants, revealed population-scale haplogroup diversity, and uncovered age-related genetic and epigenetic patterns. These results demonstrate that long-read sequencing, combined with graph-based analysis, enables integrated characterization of mitochondrial genomic and epigenomic variation. Himito is available at https://github.com/broadinstitute/Himito .
    DOI:  https://doi.org/10.1038/s41467-026-77418-y
  20. JAMA. 2026 Oct 16.
    FDA Approves a Second Weekly Basal Insulin Option for Type 2 Diabetes.
    Samantha Anderer.
      
    DOI:  https://doi.org/10.1001/jama.2026.20020
  21. Nat Commun. 2026 09 10. pii: 10690. [Epub ahead of print]17(1):
    ATAD-3 couples plasma membrane injury to mitochondrial Ca2+ signaling.
    Shiqi Xu, Yi Peng, Hengda Zhou, Xuecong Ren, Xin Wang, Zhenguang Ying, Meijiao Li, Yujie Sun, Bing Yang, Mao Zhang, Chonglin Yang, Weirui Ma, Suhong Xu.
      Mitochondrial Ca2+ uptake couples cellular Ca2+ signals to mitochondrial metabolism and stress responses and is primarily mediated by the mitochondrial Ca2+ uniporter (MCU). Here, we identify an ATAD-3-dependent mechanism that promotes mitochondrial Ca2+ uptake following plasma membrane injury in C. elegans. Living imaging reveals robust, albeit delayed, mitochondrial Ca2+ influx following injury in mcu-1 mutants, indicating the existence of a compensatory Ca2+ uptake mechanism. RNAi screen identifies the conserved AAA+ ATPase ATAD-3 as an essential regulator of this pathway, whereas MICU-3 acts as a negative regulator. Wounding induces ATAD-3 oligomerization and mitochondrial enrichment, which are enhanced in mcu-1 mutants. Disrupting ATAD-3 oligomerization or expression of disease-associated ATAD-3 variants abolishes wounding-induced mitochondrial Ca2+ uptake. Structure modeling predicts that oligomeric ATAD-3 adopts a channel-like architecture. These findings uncover ATAD-3 as a context-dependent regulator of mitochondrial Ca2+ homeostasis during cellular stress and provide insight into how this process may be disrupted in disease.
    DOI:  https://doi.org/10.1038/s41467-026-77690-y
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