bims-mithem 2025-09-14 papers

bims-mithem

Biomed News

on Mitochondria in Hematopoiesis

Issue of 2025–09–14
six papers selected by
Tim van Tienhoven, Erasmus Medical Center

Mitochondrial membrane potential and compartmentalized signaling: Calcium, ROS, and beyond.
Mitochondrial Transplantation Therapy: A Novel Approach in the Era of Organelle-Centered Regenerative Medicine.
Defective mitochondrial quality control in the aging of skeletal muscle.
Mitochondrial dysfunction in myeloid cells: a central deficit in autoimmune diseases.
Clonal Hematopoiesis in Nonmalignant Disease: Functional Consequences of Mutated Immune Cells by Clonal Hematopoiesis in the Diseased Tissue.
Unraveling the role of mitochondrial dynamics in cancer stem cells: Molecular basis and therapeutic implications.

Redox Biol. 2025 Sep 04. pii: S2213-2317(25)00372-6. [Epub ahead of print]86 103859

Mitochondrial membrane potential and compartmentalized signaling: Calcium, ROS, and beyond.

Nada Ahmed Selim, Andrew P Wojtovich.

  Mitochondria are central to cellular function, acting as metabolic hubs that regulate energy transduction to communicate cellular status. A key component of this energetic regulation is the mitochondrial membrane potential (MMP), a charge separation across the inner mitochondrial membrane generated by the electron transport chain. Beyond MMP's canonical role in driving ATP synthesis, MMP acts as a dynamic signaling hub. MMP rapidly adjusts to acute changes in cellular energy demand and undergoes sustained modifications during developmental processes, such as neuronal remodeling. Changes in MMP influence reactive oxygen species (ROS) production, calcium handling, and mitochondrial quality control, enabling localized and time-sensitive regulation of cellular function. In neurons, changes in MMP coordinate synaptic plasticity by linking metabolic state to structural changes at synapses. This review highlights the non-canonical roles of MMP in signal integration, spatial organization, and stress adaptation, providing a broader framework for understanding mitochondrial contributions to health and disease.

Keywords:  Bioenergetics; Metabolic specialization; Mitochondria; Mitophagy; Neuron plasticity

DOI:  https://doi.org/10.1016/j.redox.2025.103859
Front Biosci (Landmark Ed). 2025 Aug 18. 30(8): 37006

Mitochondrial Transplantation Therapy: A Novel Approach in the Era of Organelle-Centered Regenerative Medicine.

Ha Rim Shin, Gaheon Lee, Kyung Hwa Kim.

  Mitochondria play crucial roles in maintaining health and influencing disease progression by acting as central regulators of cellular homeostasis and energy production. Dysfunctions in mitochondrial activity are increasingly recognized as key contributors to various pathologies, ultimately impacting healthspan and disease outcomes. However, traditional treatments often do not restore damaged mitochondria to a healthy state. Mitochondrial transplantation, a cellular organelle-based therapy in which mitochondria are introduced into a recipient, has emerged as a novel concept in next-generation therapeutics that overcomes the limitations of current cell-based treatments. This review highlights the unique properties of mitochondria as therapeutic agents, including their ability to restore cellular functions and treat a wide range of diseases. In this review, we focus on the unique role of mitochondria in the regulation of stem cell functions, including stem cell fate, self-renewal, and differentiation. Various perspectives have been explored to better understand mitochondrial transplantation therapy, which harnesses the capacity of mitochondria as living drugs in regenerative medicine, as an innovative strategy to bridge the gap between cell therapy and organelle-based treatments and overcome current clinical barriers.

Keywords:  mesenchymal stem cell; mitochondrial dysfunction; mitochondrial transplantation; organelle transplantation; regenerative medicine

DOI:  https://doi.org/10.31083/FBL37006
Mech Ageing Dev. 2025 Sep 08. pii: S0047-6374(25)00088-0. [Epub ahead of print]228 112112

Defective mitochondrial quality control in the aging of skeletal muscle.

Emanuele Marzetti, Riccardo Calvani, Helio José Coelho-Junior, Francesco Landi, Anna Picca.

  Age-related skeletal muscle decline is a major contributor to frailty, functional impairment, and loss of independence in advanced age. This process is characterized by selective atrophy of type II fibers, impaired excitation-contraction coupling, and reduced regenerative capacity. Emerging evidence implicates mitochondrial dysfunction as a central mechanism in the disruption of muscle homeostasis with age. Beyond ATP production, mitochondria orchestrate redox signaling, calcium handling, and apoptotic pathways, which are increasingly compromised in aged muscle due to chronic oxidative stress and defective quality control. High-resolution respirometry has revealed intrinsic, lifestyle-independent declines in mitochondrial respiratory capacity, while large-scale phenotyping and transcriptomic profiling have established robust associations between mitochondrial integrity, physical performance, and mobility. These findings have prompted a paradigm shift from static descriptions of mitochondrial decline toward dynamic analyses of mitochondrial signaling networks and stress adaptability. Several quality control mechanisms, including mitochondrial biogenesis, dynamics, mitophagy, and vesicle trafficking, emerge as critical regulators of myocyte integrity. Understanding how these systems deteriorate with age will be pivotal for developing therapeutic targets to preserve muscle function, mitigate sarcopenia, and extend health span.

Keywords:  Autophagy; Damage associated molecular patterns; Mitochondrial DNA; Mitochondrial dynamics; Mitophagy; Myocyte; Proteasome

DOI:  https://doi.org/10.1016/j.mad.2025.112112
Trends Immunol. 2025 Sep 09. pii: S1471-4906(25)00201-7. [Epub ahead of print]

Mitochondrial dysfunction in myeloid cells: a central deficit in autoimmune diseases.

Chun-Ting J Kwong, Mariana J Kaplan.

  Autoimmune diseases arise from genetic and environmental factors that disrupt immune tolerance. Recent studies highlight the role of myeloid cell immunometabolism, particularly mitochondrial dysfunction, in driving autoimmunity. Mitochondria regulate energy homeostasis and cell fate; their impairment leads to defective immune cell differentiation, abnormal effector activity, and chronic inflammation. We propose that chronic metabolic stress reprograms myeloid cells, fueling a vicious cycle of cell death and immune activation. Over time, this may induce several states of maladaptation in myeloid cells. Viewing autoimmune disease through a metabolic lens offers new insight into disease mechanisms and highlights potential therapeutic opportunities targeting mitochondrial function to restore immune balance.

Keywords:  autoimmune diseases; mitochondrial dysfunction; myeloid cells

DOI:  https://doi.org/10.1016/j.it.2025.08.003
Annu Rev Pathol. 2025 Sep 10.

Clonal Hematopoiesis in Nonmalignant Disease: Functional Consequences of Mutated Immune Cells by Clonal Hematopoiesis in the Diseased Tissue.

Youngil Koh, Isak W Tengesdal, Siddhartha Jaiswal.

Clonal hematopoiesis, originally identified as a precursor to hematologic malignancies, has emerged as a significant factor in various nonmalignant diseases. Recent research highlights how somatic mutations in hematopoietic stem cells lead to the expansion of circulating mutated immune cells that exert profound effects on organ function and disease progression. These mutated clones display altered inflammatory profiles and tissue-specific functional consequences, contributing to various diseases including atherosclerotic cardiovascular disease, osteoporosis, heart failure, and neurodegenerative conditions. Key mutations, particularly in genes regulating epigenetics (TET2, DNMT3A, ASXL1), splicing (SF3B1, U2AF1), and DNA damage repair (TP53, PPM1D), modify immune responses and promote chronic inflammation. Intriguingly, while clonal hematopoiesis exacerbates many inflammatory conditions, it has been linked to a protective effect in Alzheimer's disease, potentially due to enhanced microglial function. Understanding the mechanistic underpinnings of clonal hematopoiesis in nonmalignant disease may inform targeted therapeutic strategies, particularly those aimed at modulating inflammation. This review explores the gene- and organ-specific roles of clonal hematopoiesis, highlighting its implications for disease pathogenesis and potential interventions.

DOI: https://doi.org/10.1146/annurev-pathmechdis-111523-023442
Biochim Biophys Acta Rev Cancer. 2025 Sep 10. pii: S0304-419X(25)00192-1. [Epub ahead of print] 189450

Unraveling the role of mitochondrial dynamics in cancer stem cells: Molecular basis and therapeutic implications.

Gaia Giannitti, Sara Marchesi, Riccardo Garavaglia, Ivan Preosto, Fabrizio Fontana.

  Many tumors consist of heterogeneous cell populations derived from a minority of cancer stem cells (CSCs), which possess distinct metabolic profiles that contribute to resistance against conventional anticancer therapy and increase the risk of tumor relapse. These unique CSC phenotypes are largely supported by altered mitochondrial function and turnover, regulated through continuous cycles of mitochondrial biogenesis, fission, fusion, and mitophagy. Consequently, understanding mitochondrial regulatory mechanisms in CSCs could reveal novel targets for cancer therapy. This article explores how mitochondrial dynamics contribute to CSC metabolic adaptation and drug resistance, alongside recent advances in the development of mitochondria-targeted drugs and their therapeutic usage.

Keywords:  Cancer stem cells; Cancer therapy; Mitochondrial biogenesis; Mitochondrial dynamics; Mitochondrial fission and fusion; Mitophagy

DOI:  https://doi.org/10.1016/j.bbcan.2025.189450