bims-mithem Biomed News
on Mitochondria in Hematopoiesis
Issue of 2026–01–04
seven papers selected by
Tim van Tienhoven, Erasmus Medical Center
  1. Linking Cell Architecture to Mitochondrial Signaling in Neurodegeneration: The Role of Intermediate Filaments.
  2. Squishing, squeezing and stretching age hematopoietic stem cells.
  3. Tregs in allogeneic hematopoietic stem cell transplantation (allo-HSCT): Suppressing GVHD While Preserving GVL.
  4. Targeting innovative therapeutic approaches to the hallmarks of aging to combat Alzheimer's disease.
  5. Shear stress governs hematopoietic stem cell fate to promote inflammation-induced aging.
  6. Ferroptosis in hematological malignancies: molecular mechanisms and therapeutic potential.
  7. Uptake mechanisms and functions of isolated mitochondria in mesenchymal stromal cells.
  1. Int J Mol Sci. 2025 Dec 08. pii: 11852. [Epub ahead of print]26(24):
    Linking Cell Architecture to Mitochondrial Signaling in Neurodegeneration: The Role of Intermediate Filaments.
    Emanuele Marzetti, Rosa Di Lorenzo, Riccardo Calvani, Hélio José Coelho-Júnior, Francesco Landi, Vito Pesce, Anna Picca.
      Mitochondrial dysfunction is a pivotal contributor to neurodegeneration. Neurons heavily rely on mitochondrial oxidative metabolism and therefore need highly efficient quality control mechanisms, including proteostasis, mitochondrial biogenesis, fusion-fission dynamics, and mitophagy, to sustain bioenergetics and synaptic function. With aging, deterioration of mitochondrial quality control pathways leads to impaired oxidative phosphorylation, excessive reactive oxygen species generation, calcium imbalance, and defective clearance of damaged organelles, ultimately compromising neuronal viability. Pathological protein aggregates, such as α-synuclein in Parkinson's disease, β-amyloid and tau in Alzheimer's disease, and misfolded superoxide dismutase 1 and transactive response DNA-binding protein 43 in amyotrophic lateral sclerosis, further aggravate mitochondrial stress, establishing self-perpetuating cycles of neurotoxicity. Such mitochondrial defects underscore mitochondria as a convergent pathogenic hub and a promising therapeutic target for neuroprotection. Intermediate filaments (IFs), traditionally viewed as passive structural elements, have recently gained attention for their roles in cytoplasmic organization, mitochondrial positioning, and energy regulation. Emerging evidence indicates that IF-mitochondria interactions critically influence organelle morphology and function in neurons. This review highlights the multifaceted involvement of mitochondrial dysfunction and IF dynamics in neurodegeneration, emphasizing their potential as targets for novel therapeutic strategies.
    Keywords:  axonal transport; cell architecture; cell quality; cytoskeleton; mitochondrial dynamics; mitochondrial quality; mitophagy; neurofilaments; neuron; reactive oxygen species
    DOI:  https://doi.org/10.3390/ijms262411852
  2. Nat Aging. 2026 Jan 02.
    Squishing, squeezing and stretching age hematopoietic stem cells.
    Chih-Ling Wang, Mary Mohrin.
      
    DOI:  https://doi.org/10.1038/s43587-025-01044-4
  3. Transplant Cell Ther. 2025 Dec 29. pii: S2666-6367(25)02654-5. [Epub ahead of print]
    Tregs in allogeneic hematopoietic stem cell transplantation (allo-HSCT): Suppressing GVHD While Preserving GVL.
    Niloufar Khayam Nekouei, Negin Najjari, Nafiseh Esmaeil, Maryam Naseroleslami, Soyar Sari, Maryam Behfar, Ali Ghamari, Hamid Farajifard, Amir Ali Hamidieh.
      Graft-versus-host disease (GVHD) is still a significant challenge for allogeneic hematopoietic stem cell transplantation (allo-HSCT), resulting in substantial non-relapse mortality. Regulatory T cells (Tregs) are essential for modulating immune responses and maintaining tolerance, resulting in a promising therapeutic approach for GVHD management. The purpose of this study is to explore the immunomodulatory effect of Tregs in preventing and managing GVHD without sacrificing the graft-versus-leukemia (GVL) effect. Preclinical and clinical studies demonstrate that ex vivo-expanded Tregs, derived from donor peripheral blood or umbilical cord blood, effectively reduce GVHD incidence when infused prophylactically. Combination therapies, including Tregs with tacrolimus or invariant natural killer T (iNKT) cell activation via α-galactosylceramide, enhance Treg's efficacy and reduce required cell doses. Improved Treg stability and in vivo expansion can be achieved through advanced strategies such as rapamycin-assisted expansion and orthogonal IL-2/IL-2Rβ systems. These findings highlight Tregs' potential to mitigate GVHD without compromising GVL, offering a biologically favorable alternative to traditional immunosuppression. Further randomized trials are needed to standardize protocols and confirm long-term efficacy in the face of challenges in Treg isolation, expansion, optimal dosing, and infusion timing, which will lead to improved transplant outcomes.
    Keywords:  GVHD; GVL; Treg; allo-HSCT; immunomodulation
    DOI:  https://doi.org/10.1016/j.jtct.2025.12.991
  4. Neural Regen Res. 2025 Dec 30.
    Targeting innovative therapeutic approaches to the hallmarks of aging to combat Alzheimer's disease.
    Michal Izrael, Orli Miriam Frenkel.
      Aging is the leading risk factor for neurodegenerative diseases, including Alzheimer's disease. Mounting evidence implicates twelve interconnected hallmarks of aging, such as genomic instability, mitochondrial dysfunction, cellular senescence, and altered intercellular communication, as core contributors to cognitive decline. In this review, we will first delineate the hallmarks of aging and their mechanistic roles according to their functions in the aging brain and Alzheimer's disease. These hallmarks can be grouped into four major functional clusters: (i) Genomic and epigenomic instability, (ii) proteostasis and organelle dysfunction, (iii) cellular fate and regenerative decline, and (iv) cellular senescence. Then, we provide an overview of innovative therapeutic approaches aimed at modifying these hallmarks, focusing on the emerging paradigm of supplementation of rejuvenation factors that are derived from young plasma, stem cell secretomes, or their derivatives (e.g., extracellular vesicles). Finally, we discuss key aging-related biological factors that can influence Alzheimer's disease progression and evaluate their potential as therapeutic targets.
    Keywords:  Alzheimer's disease; aging hallmarks; cellular senescence; genomic instability; neurodegeneration; proteostasis dysfunction; regenerative decline; rejuvenation factors; secretome
    DOI:  https://doi.org/10.4103/NRR.NRR-D-25-00966
  5. Nat Aging. 2026 Jan 02.
    Shear stress governs hematopoietic stem cell fate to promote inflammation-induced aging.
    Tongyao Shang, Li Zhao, Shibo Ying, Lida Su, Yue Yang, Jiadong Liu, Yingying Wang, Jipeng Xue, Cheng Cheng, Yixin Wu, Shiyao Chen, Hongmei Dong, Xuequn Chen, Hailin Ma, Qi Zhang, Tingbo Liang, Wei Yang, Ye Feng, Marong Fang, Xinjiang Lu.
      Hematopoietic stem cells (HSCs) reside in the bone marrow in a quiescent state, but can be mobilized into the blood in response to inflammation, cytokine stimulation, nervous activity or hypoxia. Chronic inflammation, a hallmark of aging, accelerates HSC aging by promoting myeloid-biased differentiation and reducing self-renewal capacity, yet the role of mechanical stimulation in regulating these processes remains poorly understood. Here, we found that PIEZO1 senses shear stress in blood flow to induce HSC proliferation and myelopoiesis. We show that shear stress induces PIEZO1-mediated ion currents and Ca2+ influx in both mouse and human HSCs, with downstream effects on proliferation and myeloid differentiation mediated via JAM3 and CAPN2 pathways. GsMTx4, a PIEZO1 antagonist, attenuated inflammation-induced aging in mice by inhibiting HSC activation. These findings link the mechanical sensor PIEZO1 to HSC proliferation and myeloid differentiation via multi-tiered signaling, highlighting its role in accelerating inflammation-induced aging.
    DOI:  https://doi.org/10.1038/s43587-025-01039-1
  6. Cell Oncol (Dordr). 2025 Dec 29. 49(1): 10
    Ferroptosis in hematological malignancies: molecular mechanisms and therapeutic potential.
    Jiaxi Liu, Rui Liu, Jiyu Miao, Aili He.
      Ferroptosis, an iron-dependent form of regulated cell death characterized by overwhelming accumulation of lipid peroxidation, has emerged as a prominent area of interest in cancer research. Its underlying mechanisms are complex, and the high heterogeneity of hematologic malignancies adds additional challenges. Unlike solid cancers, hematologic malignancies lack fixed tissue architecture and exist within the dynamic bone marrow microenvironment, where iron metabolism, redox balance, and lipid remodeling are uniquely regulated. These differences create distinct metabolic vulnerabilities-particularly in iron and polyunsaturated fatty acid metabolism-that may render hematologic cancer cells more sensitive to ferroptotic stress. Given these unique features, a systematic understanding of ferroptosis in hematologic malignancies is critical for both elucidating disease mechanisms and exploring novel therapeutic strategies. This review summarizes the current understanding of ferroptosis in the pathogenesis and therapeutic resistance of hematologic malignancies, highlighting its mechanistic diversity across leukemia, lymphoma, and multiple myeloma. We also discuss emerging therapeutic strategies that exploit ferroptosis and outline key challenges and future directions for translating ferroptosis-based interventions into clinical practice.
    Keywords:  Cell death; Ferroptosis; Leukemia; Lymphoma; Myeloma
    DOI:  https://doi.org/10.1007/s13402-025-01142-w
  7. Sci Rep. 2025 Dec 29. 15(1): 44799
    Uptake mechanisms and functions of isolated mitochondria in mesenchymal stromal cells.
    Mai Kanai, Miyabi Goto, Shoko Itakura, Makiya Nishikawa, Kosuke Kusamori.
      Mitochondrial transplantation holds great promise as a therapeutic strategy; however, the mechanisms by which recipient cells interact with and internalize isolated mitochondria remain unclear. Therefore, in this study, we isolated functional mitochondria from mesenchymal stromal cells (MSCs) and characterized their biological activities and physicochemical properties. Additionally, effects of isolated mitochondria on MSC functions were evaluated. Treatment with isolated mitochondria promoted cell proliferation, improved cellular viability under stress conditions, and increased the oxygen consumption rate, indicating enhanced bioenergetic capacity. Uptake of isolated mitochondria by MSCs was visualized via fluorescence imaging and quantitatively assessed over time, showing progressive internalization within 24 h. To investigate the mechanism of mitochondrial uptake, endocytosis was chemically inhibited, which revealed that endocytic pathways contributed to the internalization of the isolated mitochondria. These findings suggest that MSCs incorporate isolated mitochondria via active uptake mechanisms and that the internalized mitochondria retain their functional activity. Collectively, our results provide critical evidence of mitochondrial internalization in MSCs and offer insights into the potential applications of mitochondrial therapy for various diseases.
    Keywords:  Biomedicine; Cellular uptake; Endocytosis; Mesenchymal stromal cell; Mitochondrial transplantation
    DOI:  https://doi.org/10.1038/s41598-025-28494-5
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