bims-mithem Biomed News
on Mitochondria in Hematopoiesis
Issue of 2025–11–02
six papers selected by
Tim van Tienhoven, Erasmus Medical Center
  1. The systemic costs of hematopoietic stem cell aging.
  2. Advances in Mitochondrial Dysfunction and Its Role in Cardiovascular Diseases.
  3. Mitochondrial Dysfunction in Aging, HIV, and Long COVID: Mechanisms and Therapeutic Opportunities.
  4. Cellular Senescence and Inter-Organ Communication in Health and Disease.
  5. Autophagy-senescence interplay in kidney disease: mechanistic insights and therapeutic potential.
  6. Mitochondrial Dynamics in Blood Cancer Development and Progression.
  1. Development. 2025 Oct 15. pii: dev205103. [Epub ahead of print]152(20):
    The systemic costs of hematopoietic stem cell aging.
    Gayatri Puri, Roméo S Blanc.
      Stem cell behavior is tightly regulated by signals from the surrounding immune environment. Immune cells play an indispensable role in the maintenance, activation and differentiation of tissue-resident stem cells (TSCs). These interactions are dynamic and adapt across the lifespan, profoundly influencing regenerative capacity under both physiological and pathological conditions. Notably, immune dysfunction originating from aging hematopoietic stem cells (HSCs) disrupts tissue regeneration across distant organs, including the brain, muscle and skin. In this Review, we synthesize current knowledge on the interplay between HSC aging and TSC function, emphasizing how age-related changes in HSC-derived immune outputs impair local tissue homeostasis. We explore potential mechanisms underlying HSC-TSC communication, including inflammaging, cytokine signaling and the secretion of bioactive factors. Finally, we discuss emerging strategies aimed at rejuvenating aged HSCs, restoring immune equilibrium and enhancing systemic tissue regeneration. By linking systemic immune remodeling to local niche dysfunction, this Review proposes a hierarchical model in which HSC aging acts as a central regulator of tissue regenerative decline.
    Keywords:  Bone marrow; Hematopoietic stem cell; Immunomodulation; Immunosenescence; Inflammation; Systemic aging
    DOI:  https://doi.org/10.1242/dev.205103
  2. Cells. 2025 Oct 17. pii: 1621. [Epub ahead of print]14(20):
    Advances in Mitochondrial Dysfunction and Its Role in Cardiovascular Diseases.
    Yan Qiu, Shuo Chang, Ye Zeng, Xiaoqi Wang.
      Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide and is attributed to complex pathophysiological mechanisms that surpass the traditional risk factors. Emerging evidence indicates that mitochondrial dysfunction plays a central role in CVD progression, linking impaired bioenergetics, oxidative stress imbalance, and defective mitochondrial quality control to endothelial dysfunction, myocardial injury, and adverse cardiac remodeling. However, the mechanistic interplay between mitochondrial dysfunction and CVD pathogenesis remains unclear. This review provides a comprehensive synthesis of recent knowledge, focusing on the dysregulation of mitochondrial energy metabolism, alterations in mitochondrial membrane potential, and disruptions in mitochondrial dynamics, including the balance of fusion and fission, mitophagy, and biogenesis. Furthermore, we critically evaluated emerging mitochondria-targeted therapeutic strategies, including pharmacological agents, gene therapies, and regenerative approaches. By bridging fundamental mitochondrial biology with clinical cardiology, this review underscores the critical translational challenges and opportunities in developing mitochondria-focused interventions. A deeper understanding of the mitochondrial mechanisms in CVD pathophysiology will offer novel diagnostic biomarkers and precision-targeted therapeutics, thereby transforming CVD management.
    Keywords:  cardiovascular disease; mitochondria dynamics; mitochondrial dysfunction; mitophagy; oxidative stress; targeted therapy
    DOI:  https://doi.org/10.3390/cells14201621
  3. Pathogens. 2025 Oct 16. pii: 1045. [Epub ahead of print]14(10):
    Mitochondrial Dysfunction in Aging, HIV, and Long COVID: Mechanisms and Therapeutic Opportunities.
    María Victoria Delpino, Jorge Quarleri.
      We hypothesize that a unified mitochondrial perspective on aging, HIV, and long COVID reveals shared pathogenic mechanisms and specific therapeutic vulnerabilities that are overlooked when these conditions are treated independently. Mitochondrial dysfunction is increasingly recognized as a common factor driving aging, HIV, and long COVID. Shared mechanisms-including oxidative stress, impaired mitophagy and dynamics, mtDNA damage, and metabolic reprogramming-contribute to ongoing energy failure and chronic inflammation. Recent advancements highlight new therapeutic strategies such as mitochondrial transfer, transplantation, and genome-level correction of mtDNA variants, with early preclinical and clinical studies providing proof-of-concept. This review summarizes current evidence on mitochondrial changes across aging and post-viral syndromes, examines emerging organelle-based therapies, and discusses key challenges related to safety, durability, and translation.
    Keywords:  HIV; SARS-CoV-2; mitochondria
    DOI:  https://doi.org/10.3390/pathogens14101045
  4. Physiology (Bethesda). 2025 Oct 25.
    Cellular Senescence and Inter-Organ Communication in Health and Disease.
    Yang Zhang, Xinyue Chi, Qiulian Zhou, Shengyuan Huang, Hou-Zao Chen, Anthony Rosenzweig.
      As populations age worldwide, understanding the biology of aging and its contribution to disease becomes increasingly important. Cellular senescence, a hallmark of aging, plays a pivotal role in shaping inter-organ communication and systemic health. Once viewed primarily as a local mechanism to prevent the proliferation of damaged cells, senescence is now recognized as a dynamic, multifaceted process that influences physiology across the lifespan. Through senescence-associated secretory phenotype (SASP) proteins and other signaling modalities, including metabolites, extracellular vesicles, immune cells, and neural circuits, senescent cells contribute to both homeostatic regulation and the propagation of chronic inflammation, fibrosis, and age-related disease. These effects are often context-dependent, and senescence in one organ can influence distant tissues, driving asynchronous aging and disease vulnerability. This review examines the mechanisms by which senescent cells facilitate inter-organ communication, including emerging roles for blood-borne factors, immune cell dynamics, and neuroendocrine signals. We highlight illustrative examples of organ crosstalk and emphasize the potential translational relevance of these pathways. We also examine therapeutic strategies aimed at modulating senescence, including senolytics, senomorphics, and interventions targeting specific SASP components, as well as the potential of lifestyle modifications to mitigate biological aging. Understanding senescence and the associated inter-organ communication offers new insights into aging biology and opens promising avenues for addressing age-related diseases in an integrated, organ-spanning framework.
    Keywords:  Aging; Cellular Senescence; SASP; Senolytics; Senomorphics
    DOI:  https://doi.org/10.1152/physiol.00017.2025
  5. Mol Biol Rep. 2025 Oct 29. 53(1): 22
    Autophagy-senescence interplay in kidney disease: mechanistic insights and therapeutic potential.
    Jiajun Sang, Kexin Zhang, Qiming Fan, Chengxia Kan, Ruiyan Pan, Xiaodong Sun, Zhentao Guo.
      Autophagy and cellular senescence are intimately linked processes that play pivotal roles in renal homeostasis, aging, and disease progression. Autophagy preserves intracellular integrity by degrading damaged organelles, misfolded proteins, and metabolic waste through lysosomal pathways, thereby maintaining energy balance and delaying senescence. However, with advancing age or persistent stress, autophagic activity declines, leading to the accumulation of senescent cells, mitochondrial dysfunction, and chronic inflammation. In the kidney, a metabolically demanding organ, this imbalance contributes to the pathogenesis of chronic kidney disease (CKD) and acute kidney injury (AKI). Senescent cells secrete a senescence-associated secretory phenotype, which amplifies inflammation, fibrosis, and tissue remodeling. The bidirectional interplay between impaired autophagy and cellular senescence exacerbates renal tubular atrophy, glomerulosclerosis, and interstitial fibrosis, thereby promoting CKD progression and maladaptive repair following AKI. Emerging therapeutic strategies, including autophagy activators, senolytics, antioxidants, and stem cell based interventions, have shown promise in restoring cellular homeostasis and delaying renal aging. Nonetheless, challenges remain in achieving cell type specific modulation while avoiding the deleterious effects of excessive activation. This review highlights recent advances in understanding the mechanistic interplay between autophagy and senescence in renal physiology and disease, outlines their contributions to CKD and AKI, and explores evolving therapeutic strategies aimed at restoring autophagic flux and eliminating senescent cells. Targeting the autophagy senescence axis represents a compelling avenue for precision therapy in kidney disease and may redefine future approaches in nephrology.
    Keywords:  AKI; Autophagy; CKD; Cellular senescence
    DOI:  https://doi.org/10.1007/s11033-025-11180-0
  6. Curr Pharmacol Rep. 2025 ;11(1): 53
    Mitochondrial Dynamics in Blood Cancer Development and Progression.
    Saurav Doshi, Christina Glytsou.
       Purpose of Review: This article outlines the role of mitochondrial dynamics in healthy cells and elaborates on how blood cancer cells hijack these processes to support uncontrolled proliferation, stemness, and drug resistance. A comprehensive understanding of the mechanistic details of mitochondrial behavior in malignant hematopoiesis will provide new therapeutic avenues and improve the prediction of therapy responses.
    Recent Findings: Mitochondrial dynamics, governed by the complementary events of fusion and fission, is a key cellular process for maintaining metabolic flexibility, organelle integrity, and cellular homeostasis. Impairment of the dynamic fusion-fission balance can lead to various chronic pathologies. Recent research has highlighted how blood cancer cells exploit mitochondrial remodeling to maintain metabolic efficiency and adjust organellar quality control mechanisms to sustain survival pathways and enable cancer progression. Furthermore, leukemia and lymphoma cells use mitochondrial plasticity to adapt under stress conditions and to evade cell death induced by various clinically used or tested therapeutic regimens. Investigations using blood cancer cell lines, patient-derived samples, and xenograft models have begun to uncover the specific roles and regulatory mechanisms of mitochondrial dynamics proteins in different subtypes of hematologic malignancies, as well as in therapy resistance. Additionally, preclinical studies suggest that targeting these regulators may present novel therapeutic opportunities and serve as predictive biomarkers in blood cancers.
    Summary: This review highlights the therapeutic potential of modulating mitochondrial dynamics, underscoring the need for further integrative studies to fully harness this vulnerability in hematologic malignancies.
    Keywords:  Blood cancer; Fission; Fusion; Leukemia; Mitochondria
    DOI:  https://doi.org/10.1007/s40495-025-00431-0
This page is being maintained by Thomas Krichel. It was last updated on 2025‒11‒05 at 11:20.