bims-celmim Biomed News
on Cellular and mitochondrial metabolism
Issue of 2026–05–24
sixteen papers selected by
Marc Segarra Mondejar, AINA
  1. "SelO"ective NAD+ hydrolysis regulates mitochondrial NAD+ and homeostasis.
  2. Mitochondria across the globe: Diverse voices, shared energy.
  3. Tools and Technologies for Studying Cancer Metabolism.
  4. Biomarkers of Cancer Metabolism and Therapeutic Response.
  5. Tuning beta cells to the right frequency.
  6. Insulin receptorT1160 phosphorylation mediates renal cortical insulin resistance but not excess gluconeogenesis from glycerol.
  7. Exocytosis, Endocytosis, and Replenishment of the Immediately Releasable Pool of Secretory Vesicles. Possible Physiological Relevance in Chromaffin Cells.
  8. Endothelial Drp1 integrates VEGF-induced redox signaling with glycolysis through cysteine oxidation to drive angiogenesis.
  9. Overcoming metabolic plasticity and microenvironmental rescue when targeting SLC25A1 in acute myeloid leukemia. Comment on: "SLC25A1 reprograms mitochondrial and fatty acid metabolism to promote the progression of acute myeloid leukemia".
  10. Lipid metabolic dysregulation in diabetic kidney disease: mechanisms, cellular impact, and therapeutic strategies.
  11. MTFR2 promotes VDAC1 oligomerization to reprogram BCAA metabolism in tumor cells to polarize TAMs in LUAD.
  12. Lipopolysaccharide stimulates dynamic changes in B cell metabolism to promote proliferation.
  13. Chromatin- and actin-mediated mitochondrial streaming leads to patterning of mitochondrial distribution in oocytes.
  14. Genetic ablation of neuronal mitochondrial calcium uptake impedes Alzheimer's disease progression.
  15. Apoptosis-inducing factor starts its activity within mitochondria revealed by in situ vibrational probes.
  16. Real-time in vivo analysis of murine β cells reveals autophagic flux defects before onset of autoimmune diabetes.
  1. Cell Chem Biol. 2026 May 21. pii: S2451-9456(26)00147-9. [Epub ahead of print]33(5): 591-593
    "SelO"ective NAD+ hydrolysis regulates mitochondrial NAD+ and homeostasis.
    Qing Zhang, Trina Chia Min Tan, Vincenzo Sorrentino.
      Nicotinamide adenine dinucleotide (NAD+) is a metabolic redox cofactor whose compartmentalization in mitochondria is crucial for cellular function; however, its regulation mechanisms are largely unknown. In a recent Cell publication, Jia et al.1 uncover that the enzyme SelO catalyzes mitochondrial NAD+ hydrolysis to regulate β-oxidation and maintain mitochondrial and liver homeostasis.
    DOI:  https://doi.org/10.1016/j.chembiol.2026.04.012
  2. Cell Rep. 2026 May 21. pii: S2211-1247(26)00503-6. [Epub ahead of print]45(6): 117425
    Mitochondria across the globe: Diverse voices, shared energy.
      Like mitochondria themselves, research on this organelle can take many shapes and sizes. This month, to coincide with the Cell Press Symposia: Multifaceted Mitochondria, we are highlighting the diversity of the global mitochondria community with contributions from researchers at all career stages published across Cell Metabolism, Molecular Cell, Cell Reports, and Trends in Endocrinology and Metabolism. Together, these voices showcase the central role of mitochondrial research in metabolism, inflammation, cell biology, and much more.
    DOI:  https://doi.org/10.1016/j.celrep.2026.117425
  3. Cancer Treat Res. 2026 ;195 237-247
    Tools and Technologies for Studying Cancer Metabolism.
    Ayush Madan, Subhajit Mandal, Soukat Chandra, Joy Das, Biplab Debnath.
      Tools for studying cancer metabolism include mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy for metabolomics, metabolic imaging (PET, MRI, MRS) for in vivo analysis, and metabolic flux analysis (MFA) with stable isotope tracers to track metabolic pathways. Other technologies involve microfluidic systems for simulating tumor environments and fluorescence-activated cell sorting (FACS)-based methods for analyzing immune cell metabolism. Multiple analytical platforms that facilitate the detection of metabolites in cells and living organisms have been utilized to study cancer metabolism. In this section, we will discuss how these techniques have contributed to the study of cancer metabolism and how they have led to advances in our understanding of metabolic reprogramming and biological phenotypes.
    Keywords:  Analytical platforms; Cancer metabolism; Metabolites
    DOI:  https://doi.org/10.1007/978-3-032-21861-2_12
  4. Cancer Treat Res. 2026 ;195 193-220
    Biomarkers of Cancer Metabolism and Therapeutic Response.
    Hamid Tanzadehpanah, Ali Ahmadizad Firouzjaei, Nafiseh Izadi, Mona Mansourian, Amir Hossein Esfandiari, Khatere Mokhtari, Fatemeh Forouzanfar, Hamed Afkhami, Mahdieh Ameri Shah Reza, Mohsen Sheykhhasan, Hanie Mahaki.
      Insight into the metabolic reprogramming of cancer cells provides not only an understanding of the biology of the tumor but also novel biomarkers for diagnosis, prognosis, and therapy response monitoring. Cellular differentiation of tumors can be characterized by enhanced glycolysis, which is in accordance with changes in mitochondrial function and nutritional utilization. Elevated blood lactate and some amino acids have also been linked to tumor malignancy and unfavorable prognosis. Recent technologies, such as magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), have advanced the detection of metabolic biomarkers. These methodologies enable the comprehensive metabolic profiling of tumor tissues and body fluids, which can identify specific metabolites with the potential to be used as biomarkers. In addition, the combination of genomics and proteomics with metabolomics has offered enhanced insights into cancer metabolism and has revealed the potential for the discovery of new therapeutic targets. They have also recognized the possibility of employing noninvasive imaging methods, such as positron emission tomography using radioactively labeled metabolites, to image tumor metabolism in real time. Such imaging modalities have the potential for delivering dynamic images of metabolic events occurring during treatment and offer a potent tool for monitoring treatment response and adapting the treatment plan accordingly.This book chapter discusses the status of cancer metabolic biomarkers and their discovery from the laboratory to clinical application potential.
    Keywords:  Biomarker Discovery; Cancer Metabolism; Diagnosis; Radiotracers
    DOI:  https://doi.org/10.1007/978-3-032-21861-2_10
  5. Cell Syst. 2026 May 20. pii: S2405-4712(26)00098-0. [Epub ahead of print]17(5): 101616
    Tuning beta cells to the right frequency.
    Ryan G Hart, Mark O Huising.
      Hyperglycemia drives rolling calcium oscillations in the beta cells of the islet, which results in secretion of insulin to achieve normoglycemia. Recent work by Deng et al. examines how the beta cells' neighbors, the alpha and delta cells, determine the frequency of calcium oscillation under glucose stimulation.
    DOI:  https://doi.org/10.1016/j.cels.2026.101616
  6. Nat Commun. 2026 May 21.
    Insulin receptorT1160 phosphorylation mediates renal cortical insulin resistance but not excess gluconeogenesis from glycerol.
    Brandon T Hubbard, Yumin Ma, Rafael C Gaspar, Traci E LaMoia, Dongyan Zhang, Mario Kahn, Sylvie Dufour, Ali Nasiri, Gerald I Shulman.
      Impaired suppression of endogenous glucose production (EGP) drives end-organ damage in insulin resistance and type 2 diabetes. Although the liver is traditionally thought to mediate dysregulated EGP, the role of the renal cortex is less understood. Here, we investigate if high-fat diet (HFD) induces renal cortical insulin resistance while assessing renal glucose production (RGP) and mitochondrial metabolism in male mice. HFD increases plasma membrane sn-1,2-DAGs, PKCε translocation, and Insulin Receptor Kinase (IRK)T1160 phosphorylation while blunting insulin-stimulated pyruvate oxidation and insulin signaling. In HFD mice, RGP is elevated 6.5-fold and accounts for 60% of EGP during hyperinsulinemia. Excess RGP is derived equally from glycerol and mitochondrial sources, chiefly pyruvate. Signaling and flux defects are abrogated in HFD-fed IRKT1150A knockin mice, except for glycerol-derived gluconeogenesis. Our findings implicate the sn-1,2-DAG → PKCε → IRKT1160 axis in renal cortical insulin resistance and highlight renal gluconeogenesis as a driver of dysregulated glucose homeostasis.
    DOI:  https://doi.org/10.1038/s41467-026-73016-0
  7. J Neurochem. 2026 May;170(5): e70469
    Exocytosis, Endocytosis, and Replenishment of the Immediately Releasable Pool of Secretory Vesicles. Possible Physiological Relevance in Chromaffin Cells.
    Fernando D Marengo.
      In neuroendocrine cells, the fusion of secretory vesicles to the plasma membrane is triggered by a localized increase in cytosolic Ca2+ concentration, which occurs following the activation of voltage-dependent Ca2+ channels. However, there is an important heterogeneity in vesicle readiness for fusion because of differences in maturation, localization, and proximity to Ca2+ sources. The immediately releasable pool (IRP) was first described in rat chromaffin cells as a small group of ready-to-fuse vesicles whose fusion was tightly coupled to Ca2+ entry through voltage-dependent Ca2+ channels. Over the last 20 years, my research group has characterized several important features of IRP in chromaffin cells, including the Ca2+ channel subtype involved, the characteristics of channel-vesicle molecular coupling, the mechanisms of replenishing this pool, and the types of membrane retrieval activated after IRP exocytosis. We proposed that IRP's physiological importance lies in maintaining secretion during basal firing in chromaffin cells at rest. Here, I review the most important findings on IRP during the last 30 years, with the main focus on chromaffin cells.
    Keywords:  P/Q channels; chromaffin cells; endocytosis; exocytosis; secretion; vesicle replenishment; voltage‐dependent Ca2+ channels
    DOI:  https://doi.org/10.1111/jnc.70469
  8. Nat Commun. 2026 May 20.
    Endothelial Drp1 integrates VEGF-induced redox signaling with glycolysis through cysteine oxidation to drive angiogenesis.
    Sheela Nagarkoti, Young-Mee Kim, Archita Das, Dipankar Ash, Eric A Vitriol, Tracy-Ann Read, Varadarajan Sudhahar, Md Selim Hossain, Shikha Yadav, Stephanie Kelley Spears, Kelvin N Orji, Maritza J Romero, Rudolf Lucas, David Stepp, Eric J Belin de Chantemele, Ruth B Caldwell, David Jr Fulton, Tohru Fukai, Masuko Ushio-Fukai.
      Angiogenesis is essential for development and tissue repair after ischemia. Reactive oxygen species (ROS) act as signaling molecules that promote angiogenesis in endothelial cells (ECs) which mainly rely on aerobic glycolysis for energy production. However, how redox signaling couples to endothelial metabolism remains unclear. Here, we identify endothelial Drp1 as a redox sensor that links VEGF-induced H₂O₂ signaling to metabolic reprogramming and angiogenesis. Loss of Drp1 in ECs suppresses VEGF-driven angiogenic responses. Mechanistically, VEGF rapidly induces NOX4-dependent sulfenylation of Drp1 at Cys644, promoting disulfide bond with the metabolic kinase AMPK and subsequent oxidation of AMPK at Cys299/304 via mitochondrial fission-derived ROS. This pathway enhances endothelial glycolysis and angiogenesis. In vivo, mice with endothelial Drp1 deficiency or CRISPR-engineered redox-dead Drp1 (Cys to Ala) knock-in exhibit impaired retinal angiogenesis and post-ischemic neovascularization. Thus, endothelial Drp1 integrates mitochondrial redox signaling with glycolysis through cysteine oxidation-mediated Drp1-AMPK redox relay, thereby driving reparative neovascularization.
    DOI:  https://doi.org/10.1038/s41467-026-73128-7
  9. Haematologica. 2026 May 21.
    Overcoming metabolic plasticity and microenvironmental rescue when targeting SLC25A1 in acute myeloid leukemia. Comment on: "SLC25A1 reprograms mitochondrial and fatty acid metabolism to promote the progression of acute myeloid leukemia".
    Ruijie Li, Zhenghe Liu, Xuan Wu.
      Not available.
    DOI:  https://doi.org/10.3324/haematol.2026.301161
  10. J Clin Transl Endocrinol. 2026 May;44 100436
    Lipid metabolic dysregulation in diabetic kidney disease: mechanisms, cellular impact, and therapeutic strategies.
    You Wang, Lijia Wu, Xincui Bao, Jing Yang, Miao Xu, Yuzhuo Chang, Zhe Liu, Lingling Qin, Ming Gao, Cuiyan Lv, Tonghua Liu.
      Diabetic kidney disease (DKD) represents a prevalent and severe complication of diabetes mellitus, with growing evidence highlighting the critical role of lipid metabolic dysregulation in its pathogenesis. This review systematically examines the complex interplay between aberrant lipid metabolism and DKD progression, focusing on three major pathways: fatty acid metabolism disturbances, cholesterol homeostasis imbalance, and sphingolipid signaling alterations. We detail how these metabolic perturbations contribute to renal cell injury through multiple mechanisms, including in podocytes, tubular epithelial cells, and mesangial cells. Emerging therapeutic strategies targeting these metabolic pathways are comprehensively evaluated. Special emphasis is placed on recent advances in understanding cell-specific lipid metabolic reprogramming and its clinical implications. The review also discusses current challenges in translating these findings into clinical practice and proposes future research directions for developing personalized therapeutic approaches based on lipid metabolic profiling in DKD patients.
    Keywords:  Cholesterol; Diabetic kidney disease; Fatty acids; Lipids; Podocytes
    DOI:  https://doi.org/10.1016/j.jcte.2026.100436
  11. Cell Death Dis. 2026 May 20.
    MTFR2 promotes VDAC1 oligomerization to reprogram BCAA metabolism in tumor cells to polarize TAMs in LUAD.
    Yutong Ge, Tao Yu, Shaokun Yu, Ao Sun, Shiyu Zhang, Meiling Zhang, Qian Wang, Jia Liu, Xuan Zhang, Lulin Zeng, Kaihua Lu.
      Tumor-associated macrophages (TAMs) enriched in tumor microenvironment (TME) promote immune evasion and poor prognosis. Mitochondrial dysfunction, especially branched-chain amino acid (BCAA) metabolic reprogramming, has been confirmed to be involved in regulating TAMs function. The mitochondria-related protein MTFR2 was significantly upregulated in LUAD and closely associated with reduced survival. We conducted flow cytometry, multiplex immunofluorescence, immunohistochemistry on LUAD tissues, combined with analysis of public single-cell sequencing datasets, to characterize the TME features under MTFR2 dysregulation. Transcriptomics, metabolomics, and proteomics analyses revealed BCAA metabolic reprogramming, which was driven by MTFR2 binding to Leu125 within the β8 strand of VDAC1 and promoting its oligomerization. This interaction triggered mtDNA release into the cytoplasm, activating the TLR9-NF-κB pathway to upregulate BCAT1. Elevated concentrations of BCAA metabolites such as α-ketoisocaproate (KIC) and α-keto-β-methylvalerate (KMV) in the TME promoted M2 polarization and infiltration of TAMs by in vitro co-culture, 3D spheroid, and organoid models, and polarized M2 macrophages reciprocally promoted LUAD progression. Our findings establish a LUAD associated MTFR2-VDAC1-BCAT1 axis regulating the BCKAs-M2 axis in TAMs. Notably, targeting BCAT1 or depleting macrophages blocked this loop, offering a potential combination therapy for LUAD.
    DOI:  https://doi.org/10.1038/s41419-026-08871-2
  12. Elife. 2026 May 21. pii: RP109093. [Epub ahead of print]14
    Lipopolysaccharide stimulates dynamic changes in B cell metabolism to promote proliferation.
    Dana M S Cheung, Momchil Razsolkov, Fabrizia Bonacina, Stephen Andrews, Megan C Sumoreeah, Linda V Sinclair, Andrew J M Howden, J Simon C Arthur.
      Naive B cells exit quiescence and enter a proliferative state upon activation, ultimately differentiating into antibody-secreting or memory B cells. Toll-like receptor (TLR) ligands, such as lipopolysaccharide (LPS), can serve as physiological stimuli to initiate this transition. Using quantitative proteomics, we show that TLR4 engagement induces metabolic reprogramming in murine B cells, increasing the expression of amino acid transporters and cholesterol biosynthetic enzymes. The amino acid transporter SLC7A5 is markedly upregulated following LPS stimulation, and conditional deletion of Slc7a5 impairs B cell proliferation, underscoring its essential role in B cell activation. LPS also elevates intracellular cholesterol levels, and inhibition of the rate-limiting enzyme HMG-CoA reductase blocks proliferation. This effect was mediated by a dual requirement for cholesterol metabolism and protein prenylation downstream of HMG-CoA reductase. Notably, this was not unique to TLR4 signalling but is also observed in B cells activated via TLR7, TLR9, CD40, or the B cell receptor. Together, these findings reveal that metabolic rewiring, including amino acid uptake and cholesterol metabolism, is an essential feature of B cell activation and proliferation.
    Keywords:  B cell; cholesterol; immunology; inflammation; mouse; statin; toll-like receptor
    DOI:  https://doi.org/10.7554/eLife.109093
  13. Nat Commun. 2026 May 18.
    Chromatin- and actin-mediated mitochondrial streaming leads to patterning of mitochondrial distribution in oocytes.
    In-Won Lee, Morteza Nazari, Jazmine Yuson, Sanjeev Uthishtran, Ross Stocker, Deepak Adhikari, Zhong-Wei Wang, Gyorgy Szabadkai, Michael R Duchen, Senthil Arumugam, Reza Nosrati, John Carroll.
      Mitochondria are highly dynamic organelles, and their spatiotemporal organization is strictly regulated. While it has long been recognized that mitochondria in ovulated oocytes are concentrated in the spindle hemisphere, the mechanism remains unknown. Through live cell imaging and modeling, we have discovered that mitochondrial polarization in MII oocytes is achieved through two distinct mechanisms: (i) a mechanism in which mitochondria are transported by actin-driven cytoplasmic streaming that is delimited to the spindle hemisphere; (ii) an active, MYO19 dependent channeling mechanism that directs mitochondria from beneath the spindle to the polarized cortex bilaterally and perpendicular to the long axis of the MII spindle. This directionality in mitochondrial streaming patterns the ooplasm of the spindle hemisphere, creating mitochondria-rich and mitochondria-poor regions. These features explain the establishment of the polar gradient of mitochondria in MII oocytes and may provide new insight into the spatiotemporal organization of mitochondria in cells.
    DOI:  https://doi.org/10.1038/s41467-026-73192-z
  14. EMBO J. 2026 May 22.
    Genetic ablation of neuronal mitochondrial calcium uptake impedes Alzheimer's disease progression.
    Pooja Jadiya, Elena Berezhnaya, Devin W Kolmetzky, Dhanendra Tomar, Henry M Cohen, Shatakshi Shukla, Manfred Thomas, Salman Khaledi, Joanne F Garbincius, Liam Kennedy, Oniel Salik, Darpan Raghav, Alycia N Hildebrand, John W Elrod.
      Loss of mCa2+ efflux capacity contributes to the pathogenesis and progression of Alzheimer's disease (AD) by promoting mitochondrial Ca2+ (mCa2+) overload. Here, we utilized loss-of-function genetic mouse models to causally evaluate the role of mCa2+ uptake by conditionally deleting the mitochondrial calcium uniporter channel (mtCU) in a robust mouse model of AD. Loss of neuronal mCa2+ uptake reduced Aβ and tau-pathology, synaptic dysfunction, and cognitive decline in 3xTg-AD mice. Knockdown of Mcu in an in vitro model of AD significantly reduced matrix Ca2+ content, redox imbalance, and mitochondrial dysfunction. The preservation of mitochondrial function rescued the AD-dependent decline in autophagic capacity and protected neurons against amyloidosis and cell death. This was corroborated by in vivo data showing improved mitochondrial structure and apposition in AD mice with loss of neuronal Mcu. These results suggest that inhibition of neuronal mCa2+ uptake represents a powerful therapeutic target to impede AD progression.
    DOI:  https://doi.org/10.1038/s44318-026-00809-w
  15. Proc Natl Acad Sci U S A. 2026 May 26. 123(21): e2528689123
    Apoptosis-inducing factor starts its activity within mitochondria revealed by in situ vibrational probes.
    Jinyu Zhu, Yi Liao, Mengfan Feng, Li Song, Wei Li, Linjun Cai, Xiao Xia Han.
      Apoptosis-inducing factor (AIF) is a flavoprotein located in the mitochondrial intermembrane space, and it is believed to trigger caspase-independent cell death after its release from the mitochondria into the nucleus. Here, the proapoptotic activity of AIF within mitochondria and the underlying molecular mechanism are explored using label-free vibrational spectroscopy and imaging. Electron transfer between AIF and cytochrome c (Cyt c) is evidenced by resonance Raman spectroscopy, and the details of their interaction are revealed through molecular dynamics simulations. We elucidate the nicotinamide adenine dinucleotide (NADH)-AIF-dependent generation of reactive oxygen species (ROS) and its correlation with phospholipid peroxidation at the molecular level. With in situ Raman probes, our results verified the synergistic contribution of AIF and Cyt c to mitochondrial membrane permeabilization via a ROS-independent pathway. Remarkably, NADH-dependent Cyt c release from isolated mitochondria is clearly monitored by in situ and real-time Raman spectroscopy, and our findings prove the proapoptotic role of NADH, further supported by flow cytometry. This function of AIF has implications for a deeper understanding of cell death executors and would open up therapeutic strategies for cancer.
    Keywords:  apoptosis; apoptosis-inducing factor; cytochrome c; electron transfer; phospholipid peroxidation
    DOI:  https://doi.org/10.1073/pnas.2528689123
  16. Sci Transl Med. 2026 May 20. 18(850): eadj4902
    Real-time in vivo analysis of murine β cells reveals autophagic flux defects before onset of autoimmune diabetes.
    Olha Melnyk, Charanya Muralidharan, Bryce E Duffett, Alissa N Muncy, Leslie E Wagner, Matthew Austin, Jahnavi Aluri, Abdul S Qadir, Yashaswini Battina, Rachael Morara, Glorian Perez-Aviles, Justin J Crowder, Michelle M Martinez-Irizarry, Sylvaine You, Roberto Mallone, Amelia K Linnemann.
      Autophagy, a vital catabolic process, plays a crucial role in maintaining pancreatic β cell function and is disrupted in established type 1 diabetes. However, it is unclear when and how this critical cell process becomes defective during type 1 diabetes pathogenesis. To study the nature of autophagy dysfunction in the context of autoimmune diabetes, we used real-time intravital microscopy to study autophagic flux in vivo. We generated an AAV8-packaged mCherry-eGFP-LC3B biosensor driven by the insulin promoter for β cell-selective expression. For real-time autophagic flux evaluation, fluorescent signals from eGFP and mCherry fluorophores were correlated in space and time to follow the process of autophagosome-lysosome fusion. We observed autophagic flux defects in the β cells of the nonobese diabetic (NOD) mouse model of type 1 diabetes before hyperglycemia onset at both baseline and in response to interferon-α. These defects were still present, although less apparent, in immunodeficient NOD/scid/il2rg (NSG) mice. We also observed heterogeneous autophagic flux in human donor islets transplanted under the kidney capsules of NSG mice. In sum, the ability to visualize autophagic flux in β cells over time in vivo revealed impairments in those β cells that preceded the onset of autoimmune diabetes.
    DOI:  https://doi.org/10.1126/scitranslmed.adj4902
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