bims-mithem 2025-08-24 papers

bims-mithem

Biomed News

on Mitochondria in Hematopoiesis

Issue of 2025–08–24
eight papers selected by
Tim van Tienhoven, Erasmus Medical Center

Mitochondrial Quality Control in Health and Disease.
High tide or low tide: the transport and metabolism of mitochondrial nucleotides.
Significance of Mitochondrial Dynamics in Reproductive Physiology: Current and Emerging Horizons in Mitochondrial Therapy for Assisted Reproductive Technologies.
The emerging role of cellular senescence in amyotrophic lateral sclerosis.
Biomimetic artificial bone marrow niches for the scale up of hematopoietic stem and progenitor cells.
Reasonable Design of Near-Infrared Boron Dipyrromethene with Cationic Pyridinium for Super-Resolution Imaging of Dynamic Voltages of Mitochondria in Living Cells.
Mitotherapy Restores mitochondrial function and improves cognitive deficits in Alzheimer's disease.
Progress in stem cells mitochondrial proteomics research: A review.

MedComm (2020). 2025 Aug;6(8): e70319

Mitochondrial Quality Control in Health and Disease.

Lin Ye, Xinzhi Fu, Qi Li.

  Mitochondria are central regulators of cellular energy metabolism, and their functional integrity is essential for maintaining cellular homeostasis. Mitochondrial quality control (MQC) encompasses a coordinated network of mitochondrial biogenesis, dynamics (fusion and fission), and selective autophagy (mitophagy), which together sustain mitochondrial structure and function. Under physiological conditions, MQC ensures the removal of dysfunctional mitochondria, restricts excessive reactive oxygen species production, and modulates apoptosis, thereby supporting the high energy demands of organs such as the heart and brain. Disruption of MQC contributes to the onset and progression of various diseases, including neurodegenerative disorders, cardiovascular pathologies, and metabolic syndromes, largely through accumulation of damaged mitochondria and impaired metabolic signaling. While the core components of MQC have been characterized, the mechanistic interplay among its modules and their disease-specific alterations remain incompletely defined. This review provides an integrated overview of the molecular pathways governing mitochondrial biogenesis, dynamics, and mitophagy, with a focus on their cross-talk in maintaining mitochondrial homeostasis. We further discuss how MQC dysfunction contributes to disease pathogenesis and examine emerging therapeutic approaches aimed at restoring mitochondrial quality. Understanding the regulatory logic of MQC not only elucidates fundamental principles of cellular stress adaptation but also informs novel strategies for disease intervention.

Keywords:  disease intervention; mitochondria; mitochondrial quality control; therapeutic strategies

DOI:  https://doi.org/10.1002/mco2.70319
Biochem J. 2025 Aug 18. pii: BCJ20253237. [Epub ahead of print]482(16):

High tide or low tide: the transport and metabolism of mitochondrial nucleotides.

Thomas MacVicar.

  Mitochondria are multifaceted organelles that support numerous cellular metabolic pathways, including the biosynthesis of nucleotides required for cell growth and proliferation. Owing to an ancient endosymbiotic origin, mitochondria contain multiple copies of their own genome and therefore demand sufficient (deoxy)nucleotides in the mitochondrial matrix for DNA replication and transcription into RNA. Disturbed mitochondrial deoxynucleotide homeostasis can lead to a decline in mitochondrial DNA abundance and integrity, causing mitochondrial diseases with diverse and severe symptoms. Mitochondrial nucleotides are not only required for nucleic acid synthesis but also for bioenergetics and mitochondrial enzymatic activity. This review first explores how mitochondria supply energy and anabolic precursors for nucleotide synthesis and how the mitochondrial network influences the spatial control of cellular nucleotide metabolism. Then follows an in-depth discussion of the mechanisms that supply mitochondria with sufficient and balanced nucleotides and why these mechanisms are relevant to human mitochondrial disease. Lastly, the review highlights the emergence of regulated mitochondrial nucleotide supply in physiological processes including innate immunity and discusses the implications of dysregulated mitochondrial and cytosolic nucleotide homeostasis in pathophysiology.

Keywords:  metabolism; mitochondria; mitochondrial disease; nucleotide salvage; nucleotide transport; nucleotides

DOI:  https://doi.org/10.1042/10.1042/BCJ20253237
Reprod Med Biol. 2025 Jan-Dec;24(1):24(1): e12672

Significance of Mitochondrial Dynamics in Reproductive Physiology: Current and Emerging Horizons in Mitochondrial Therapy for Assisted Reproductive Technologies.

Sanath Udayanga Kankanam Gamage, Yoshiharu Morimoto.

   Background: Mitochondria play a critical role in cellular bioenergetics and signaling, with particular importance in the context of reproductive biology. This review summarizes their role in reproduction and explores current and emerging mitochondrial therapies for fertility treatment.
Methods: A comprehensive literature search using terms like mitochondria, infertility, reproduction, gametes, mitochondrial replacement, and mitochondrial transplantation identified relevant studies on mitochondria's role in gametogenesis, fertilization, and early embryonic development in relevant databases. Selected publications were reviewed and summarized to present current and future mitochondrial therapies for fertility.
Main Findings: Mitochondrial dynamics and functions are critical for meeting the energy requirements of essential reproductive processes, including gametogenesis, fertilization, and early embryonic development. Dysregulation of mitochondrial function has been associated with a range of reproductive disorders, such as infertility, recurrent pregnancy loss, and maternally inherited mitochondrial diseases. Emerging therapeutic strategies, such as mitochondrial replacement therapy, antioxidant supplementation, and mitochondrial transplantation, offer promising avenues for overcoming these challenges and improving reproductive outcomes.
Conclusions: Utilizing mitochondrial-based therapies represents a promising and innovative approach in the advancement of fertility treatments. Ongoing research and clinical development in this area hold significant potential to enhance reproductive outcomes and improve the quality of life for individuals and couples facing fertility challenges.

Keywords:  ascent; infertility; mitochondria; mitochondrial dysfunction; mitochondrial therapies for infertility; mitochondrial transplantation; reproductive aging

DOI:  https://doi.org/10.1002/rmb2.12672
Front Neurosci. 2025 ;19 1599492

The emerging role of cellular senescence in amyotrophic lateral sclerosis.

Xingli Tan, Naiyong Gao.

  Cellular senescence is a state of permanent cell cycle arrest and is considered a key contributor to aging and age-related diseases, including amyotrophic lateral sclerosis (ALS). The physiological processes of aging lead to a variety of molecular and cellular phenotypes, and evidence of overlap between ALS and aging-related biomarkers suggests that cell type-specific senescence may be a critical factor in ALS. Senescent microglial cells, astrocytes, and neurons have been detected in ALS patients and animal models. However, while accumulating evidence suggests a potential link between cellular senescence and ALS, this connection remains not yet conclusively established. Importantly, how senescent cells may contribute to the neuropathophysiology of ALS remains largely unknown. Additionally, the growing popularity of anti-aging therapies has highlighted the potential of senescent cell clearance as a promising strategy for treating age-related diseases, including ALS. This review provides an overview of cellular senescence, discusses recent advances in understanding how senescence in different cell types influences ALS pathogenesis, and explores the potential role of anti-senescence therapies in ALS treatment.

Keywords:  aging; aging of motor neurons; amyotrophic lateral sclerosis; anti-senescence; cellular senescence

DOI:  https://doi.org/10.3389/fnins.2025.1599492
Biomaterials. 2025 Aug 08. pii: S0142-9612(25)00531-9. [Epub ahead of print]325 123612

Biomimetic artificial bone marrow niches for the scale up of hematopoietic stem and progenitor cells.

Minerva Bosch-Fortea, Daniele Marciano, Julien E Gautrot.

  Hematopoietic stem cell (HSC) transplantation to treat haematological disorders is greatly restricted by poor cell availability. Engineering of culture platforms that mimic the physiological properties of the bone marrow (BM) in a scalable format is important to enable the translation of HSC therapies. Here, we report the design of biomimetic BM niches enabling the culture of HSCs in a scalable 3D platform. Beyond cellular and biochemical components (e.g. matrix and growth factors), an important element of the BM microenvironment is its architecture, dense in adipocytes, with relatively limited matrix and anisotropic mechanical properties. To capture this context, we propose the use of bioemulsions1,2 in which oil microdroplets and associated mechanical anisotropy recreate important architectural features of the hematopoietic niche. Mesenchymal stem cells (MSCs) grown at the surface of bioemulsions assembled an interstitial matrix and secreted important factors critical to the maintenance of HSC phenotype. HSCs cultured in the resulting artificial BM niches maintained stemness whilst expanding significantly (>33-fold compared to suspension cultures) and enabling scale up of expansion in conical flask bioreactors (2 M cell batches). This platform harnesses engineered BM microenvironments and the processability of microdroplet technologies to produce HSCs in a scalable format, for application in cell-based therapies.

Keywords:  2D nanomaterials; Liquid-liquid interface; Protein nanosheet; Self-assembly; Stem cells; Toughness

DOI:  https://doi.org/10.1016/j.biomaterials.2025.123612
ACS Sens. 2025 Aug 17.

Reasonable Design of Near-Infrared Boron Dipyrromethene with Cationic Pyridinium for Super-Resolution Imaging of Dynamic Voltages of Mitochondria in Living Cells.

Jiang-Lin Wang, Lu Zhang, Huan He, Pengfei Zhang, Feng-Lei Jiang.

  Mitochondrial membrane potential (ΔΨm) is a critical regulator of cellular homeostasis and an established biomarker in mitochondrial dysfunction. While super-resolution fluorescence imaging reveals intrinsic links between mitochondrial ultrastructure and function, prolonged monitoring of the dynamic ΔΨm remains constrained by the scarcity of photostable voltage-sensitive probes. Here, we designed and synthesized three water-soluble near-infrared boron dipyrromethene (BODIPY) probes (o/m/pMePy-BDP). These cationic pyridinium-functionalized probes exhibit specific mitochondria localization (Pearson's colocalization coefficient >0.93), high photostability (<15% intensity loss after 15 min laser irradiation), and exceptional biocompatibility. When integrated with structured illumination microscopy (SIM), they resolved mitochondrial cristae ultrastructure at 0.24 μm resolution and captured real-time ΔΨm fluctuations during fusion/fission (∼15 mV shifts) and mitochondria-lysosome contact (MLC). Semiquantitative submitochondrial models further revealed voltage gradients (150-170 mV) across cristae junctions, challenging the classical "homogeneous ΔΨm" paradigm. The probes' compatibility with multiplexed imaging enabled continuous ΔΨm tracking during mitophagy, uncovering transient bioenergetic hotspots. This work bridges nanoscale mitochondrial dynamics to disease mechanisms, providing tools to dissect pathologies from neurodegeneration to cancer.

Keywords:  BODIPY; SIM; fluorescent probes; organelle dynamics; voltage-sensitive imaging

DOI:  https://doi.org/10.1021/acssensors.5c01636
Mitochondrion. 2025 Aug 15. pii: S1567-7249(25)00074-1. [Epub ahead of print] 102077

Mitotherapy Restores mitochondrial function and improves cognitive deficits in Alzheimer's disease.

Tulika Gupta, Asha Rao, Veena Devi, Lalita Kumari, Akshita Negi, Munish Kumar, Ranjana Bharti, Bikash Medhi.

  Mitochondrial dysfunction is a hallmark of Alzheimer's disease (AD), contributing to cognitive decline. This study explores the therapeutic potential of mitochondrial transplantation in mitigating cognitive decline in AD. Structurally and functionally characterized mitochondria from young rat brains were intravenously transplanted into AD rats. Confocal imaging confirmed integration of exogenous tagged mitochondria into hippocampal tissue. Post-mitotherapy, we noted significant cognitive improvement by neurobehavioral tests and significant reduction in protein levels of amyloid precursor protein. Further mitochondrial functional parameters improved; reduced oxidative stress, improved mitochondrial membrane potential, and calcium homeostasis. These findings highlight mitotherapy as a promising strategy for treating Alzheimer's disease.

Keywords:  AD Rat model; Alzheimer’s disease (AD); Cognitive improvement; Mitochondrial dysfunction; Mitotherapy

DOI:  https://doi.org/10.1016/j.mito.2025.102077
Adv Clin Exp Med. 2025 Aug 19.

Progress in stem cells mitochondrial proteomics research: A review.

Weidong Yao, Xinyi Yu, Yameng Wang, Liang Xia.

  This review summarizes the latest advancements in stem cell (SC) mitochondrial proteomics. With the rapid development of biotechnology, mitochondrial proteomics has emerged as a pivotal area in SC research. The research methods used in mitochondrial proteomics include mass spectrometry (MS), with pre-MS sample processing, MS data acquisition employing both qualitative and quantitative approaches, and bioinformatics analysis to annotate and explore protein functions. In recent years, mitochondrial proteomics research has contributed to the establishment and expansion of our understanding of the roles of various mitochondrial proteins involved in regulating SC differentiation, metabolism and aging, including Drp1, Mfn1/2, OPA1, SIRT3, Bcl-2, YME1L, and PGC-1α. This multidisciplinary approach, combining qualitative and quantitative proteomics with bioinformatics, sheds light on the intricate regulatory mechanisms of mitochondrial proteins in SC. These findings provide a scientific basis for developing novel therapeutic targets and strategies, thereby advancing the field of regenerative medicine and personalized treatment paradigms.

Keywords:  bioinformatics; mass spectrometry; mitochondria; proteomics; stem cells

DOI:  https://doi.org/10.17219/acem/203862