bims-mitrat 2026-05-24 papers

bims-mitrat

Biomed News

on Mitochondrial transplantation and transfer

Issue of 2026–05–24
thirteen papers selected by
Gökhan Burçin Kubat, Başkent Üni̇versi̇tesi̇

Restoration of neuromuscular function by mitochondrial transplantation in injured mouse skeletal muscle.
Fabrication of fusogenic and magnet-responsive cells for transplantation of an intact mitochondrial network.
Mitochondria transfer in neurological disorders: the key role of neuroglia.
Reparative "exosome-ark" for mitochondrial transplantation to reprogram macrophages and disrupt pathogenic crosstalk in pulmonary fibrosis.
Mitochondrial Dynamics and Transfer in Mesenchymal Stromal Cells: Redox Regulation, Therapeutic Mechanisms, and Engineering Strategies.
Neutrophil-Like Mitochondria Enable Blood-Brain Barrier Transmigration and Neuroprotection.
Nano- and Microtubes: Tiny Fusion Events but Not Overall Plasma Membrane Merger for Exchanging Intracellular Components.
Mitochondrial micro-nano reactors via enhancing mitochondrial transfer and mitophagy for alleviating metabolic crisis.
The progress of mitochondrial function and transfer in stem cell regulation and therapy.
Mitochondrial metabolic reprogramming, quality control, and intercellular transfer in regulating macrophage plasticity.
Xenogeneic Mitochondrial Transplantation Improves Selected Age-Associated Phenotypes in Mice.
Novel Organelle-Based Intracellular Immunity with Mechanistic and Therapeutic Implications.
Stress-triggered cell elimination stabilizes resource-limited cell collectives: An agent-based model.

J Physiol. 2026 May 21.

Restoration of neuromuscular function by mitochondrial transplantation in injured mouse skeletal muscle.

Stephen E Alway, Peter J Ferrandi, Hector G Paez, Christopher R Pitzer, Junaith S Mohamed, Michael R Deschenes, James A Carson.

  Rehabilitative activity can improve injury repair, but it risks additional damage and reduces the functional recovery of regenerating muscle. This study tested the hypothesis that moderate electrically evoked contractions would slow restoration of neuromuscular function after cardiotoxin-induced injury; however exogenous mitochondrial transplantation (MT) would enhance recovery of contractile function after injury. Cardiotoxin was injected into the tibialis anterior of C57BL/6 mice (10-12 weeks of age) to induce muscle necrosis. Exogenous mitochondria or phosphate-buffered saline (PBS) were injected into the mouse tail vein after cardiotoxin injury. Injured muscles were either rested or given 40 Hz submaximal electrically evoked contractions to cardiotoxin-injured muscles during the recovery period. Relative to intra-animal non-damaged control muscles restoration of peak tetanic torque after both rested and evoked contractions during recovery and twitch torque was greater, and the difference between control and injured muscle twitch one-half relaxation time was lower in injured muscles that were rested for 10 days after injury and received MT compared to PBS-treated muscles. Neuromuscular junction efficiency in cardiotoxin-injured muscles was ∼70% of control undamaged muscles, but MT improved the recovery of neuromuscular junction efficiency to produce torque by 14 days after cardiotoxin injury in muscles that received additional damage induced by evoked contractions during the recovery period. These data suggest that MT enhances the recovery of neuromuscular function when the muscle is rested after injury, but it provides limited improvement in muscle function when the muscle is challenged with electrically evoked contractions in the recovery period after injury. KEY POINTS: Mitochondrial transplantation by systemically infusing healthy donor mitochondria into injured mice improved the recovery of maximal torque production of injured muscles when evoked contractions were provided to the regenerating muscle during the recovery period after injury. Mitochondrial transplantation improved the restoration of neuromuscular junction efficiency after muscle injury. The recovery of maximal torque capabilities function following cardiotoxin-induced tibialis anterior muscle injury was attenuated by electrically evoked muscle contractions conducted every other day during the recovery period in young adult mice.

Keywords:  mitochondria; muscle contractile properties; muscle injury; neuromuscular junction; regeneration

DOI:  https://doi.org/10.1113/JP290801
Acta Biochim Biophys Sin (Shanghai). 2026 May 11.

Fabrication of fusogenic and magnet-responsive cells for transplantation of an intact mitochondrial network.

Liqun Xu, Xiao Li, Xing Fan, Wei Yan, Wanfei Wu, Junwei Li, Ronghao Deng, Haibao Zhu, Aihua Mao, Pingnan Sun, Xin Zhang, Wencan Xu, Chi-Ju Wei.

  Mitochondrial transplantation is a promising treatment for many diseases associated with mitochondrial defects or aging; however, a reliable method for mitochondrial transfer remains urgently needed. In this study, we assemble fusogenic and magnet-responsive cells (FMRCs), which are enucleated stem cells loaded with Fe 3O 4 nanoparticles and further incorporated fusogenic vesicular stomatitis virus glycoprotein G (VSV-G). Mitochondrial transplantation from FMRCs via fusion in the presence of a magnetic force restores normal mitotic activity, mitochondrial membrane potential, ROS levels and ATP production in cells subjected to partial mtDNA depletion or in cybrids harboring mtDNA with a 4977-bp deletion. SNP tracing and qPCR analysis of the mitochondrial and nuclear genomes unequivocally demonstrate that exogenous mitochondria are able to reside stably and predominately. Mitochondrial transplantation stimulate autophagy and thus the clearance of defective endogenous counterparts, resulting in lower mtDNA heteroplasmy. These results suggest that FMRCs are excellent vehicles for mitochondrial transplantation and could be used for the treatment of aging and mitochondria-associated diseases.

Keywords:  143B cell; SNP analysis; VSV-G; autophagy; cell fusion; fusogenic and magnet-responsive cell; mitochondrial transplantation

DOI:  https://doi.org/10.3724/abbs.2026031
Mol Neurodegener. 2026 May 21.

Mitochondria transfer in neurological disorders: the key role of neuroglia.

Jie Jiao, Hui Chen, Alexei Verkhratsky, Yixun Su, Chenju Yi.

  Mitochondria transfer has emerged as a distinctive mechanism for intercellular communication and neuronal homeostasis. Neurones, owing to their unique bioenergetic demands, are particularly vulnerable to mitochondrial dysfunction, a shared pathogenetic feature across many neurological conditions, including neurodegenerative disorders, cerebrovascular diseases, and brain injuries. Intercellular transfer of mitochondria represents a potential adaptive mechanism rectifying compromised mitochondrial function. Neuroglial cells, especially astrocytes and microglia, frequently act as mitochondrial donors, supplying functional mitochondria to stressed neurones to restore bioenergetic capacity and influence disease trajectories. However, mitochondria transfer is intrinsically context dependent and can exert opposing effects. In addition to providing metabolic support, damaged mitochondria may also be transferred, propagating pathological signals, and exacerbating tissue injury. Moreover, in advanced disease states, mitochondrial malfunction often affects all cell types in the nervous system, including neuroglia, limiting the availability of healthy endogenous mitochondrial donors. This review critically examines mitochondria transfer in neurological diseases, with a focus on glial contribution and underlying mechanisms, and outlines key challenges and opportunities for advancing both mechanistic understanding and therapeutic translation.

Keywords:  Ageing; Extracellular vesicles; Mitochondrial transplantation; Neurodegeneration; Neuroglia; Traumatic brain injury; Tunnelling nanotubes

DOI:  https://doi.org/10.1186/s13024-026-00953-1
Mater Today Bio. 2026 Jun;38 103201

Reparative "exosome-ark" for mitochondrial transplantation to reprogram macrophages and disrupt pathogenic crosstalk in pulmonary fibrosis.

Xin-Yue Zhang, Yi-Na Liu, Bo Wang, Chen-Guang Zhang, He-Qi Cheng, Xing-Rong Yang, Jin-Huan Wan, Xue-Cheng Sheng, Bin Guo, Hu-Lin Jiang, Xin Chang.

  Pulmonary fibrosis (PF) progresses through a vicious cycle of crosstalk between injured alveolar epithelial cells II (AECs II) and alveolar macrophages. While mitochondrial transplantation offers a promising cure for macrophage metabolic dysfunction, the efficacy is hampered by poor targeting and rapid loss of mitochondrial integrity in vivo. Herein, we engineered a hierarchical strategy that integrates biomanufacturing, organelle protection and metabolic reprogramming. Initially, we utilized a "hijacking" strategy for manufacturing, where lipid nanoparticles (LNPs) delivering a mitochondrial-targeting sirtuin 3 plasmid (pMTS-SIRT3) rejuvenated injured AECs II, transforming them into factories for reparative exosomes. These harvested vesicles were then engineered into an "Exosome-Ark" by encapsulating healthy mitochondria. The pro-reparative intra-exosomal microenvironment functions as a cytoplasm-like milieu to maintain the biological activity of the isolated mitochondria, while mannose functionalization ensured macrophage-specific targeting. In bleomycin (BLM)-induced PF mice model, "exosomes-ark" restored macrophage mitochondrial homeostasis through enhanced fusion-fission dynamics and metabolic reprogramming, suppressed transforming growth factor-β (TGF-β) expression, and attenuated myofibroblast activation. Mechanistically, exosomal reparative signals promoted macrophages for mitochondrial engraftment, revealing a synergistic effect beyond simple organelle replacement. This study presented a biologically inspired platform, offering a translational potential for treating fibrotic diseases driven by AECs II-immune cell crosstalk.

Keywords:  Engineered exosomes; Exosome-ark; Macrophage reprogramming; Pathogenic crosstalk; Pulmonary fibrosis; Safe mitochondria transplantation

DOI:  https://doi.org/10.1016/j.mtbio.2026.103201
Free Radic Biol Med. 2026 May 20. pii: S0891-5849(26)00771-9. [Epub ahead of print]

Mitochondrial Dynamics and Transfer in Mesenchymal Stromal Cells: Redox Regulation, Therapeutic Mechanisms, and Engineering Strategies.

XueXia Liu, XiaoXin Wang, FuJun Liu.

  Mesenchymal stromal cells (MSCs) are metabolically active and redox-sensitive therapeutic cells, with their therapeutic potency tightly linked to mitochondrial integrity and function. Beyond paracrine and immunomodulatory actions, MSCs can transfer functional mitochondria to damaged cells, restoring bioenergetics, maintaining redox homeostasis via ROS regulation, and facilitating tissue repair and regeneration. This review summarizes recent progress in MSC mitochondrial biology, highlighting how metabolic reprogramming, mitochondrial biogenesis, fusion-fission dynamics and mitophagy coordinately regulate MSC stemness, differentiation, senescence and therapeutic capacity. It outlines core redox regulatory networks covering mitochondrial ROS production (ETC Complexes I/III and reverse electron transport), non-mitochondrial oxidases (NADPH oxidases), and canonical antioxidant signaling (Nrf2/Keap1, thioredoxin/peroxiredoxin and glutathione/glutaredoxin). Redox-dependent post-translational modifications governing mitochondrial transfer machinery are emphasized, including cysteine oxidation of connexin 43, redox-regulated Drp1 phosphorylation, and oxidative modulation of Miro1-mediated mitochondrial trafficking. Major intercellular mitochondrial transfer routes, such as tunneling nanotubes, connexin 43-based intercellular communication and extracellular vesicles, are discussed under inflammatory, hypoxic and metabolic stress conditions. Preclinical studies across pulmonary, cardiovascular, neurological, renal, hepatic and immune-mediated diseases validate that MSC-derived mitochondrial transfer preserves ATP production, mitigates oxidative injury and remodels recipient cell immunometabolic phenotypes. Emerging engineering strategies to improve mitochondrial delivery and therapeutic outcomes are also reviewed, alongside translational bottlenecks including cell source heterogeneity, mitochondrial quality control, in vivo tracking, dosage optimization and long-term biosafety. Overall, MSC mitochondrial dynamics and intercellular transfer bridge redox biology, metabolism and regenerative medicine, offering mechanistic insights for next-generation precision regenerative therapies.

Keywords:  Extracellular vesicles; Mesenchymal stromal cells; Mitochondrial transfer; Redox homeostasis; Regenerative medicine

DOI:  https://doi.org/10.1016/j.freeradbiomed.2026.05.291
ACS Nano. 2026 May 18.

Neutrophil-Like Mitochondria Enable Blood-Brain Barrier Transmigration and Neuroprotection.

Namjo Shin, Yina Wu, Jinwon Park, Junho Byun, Seongsoo Lee, Wooin Lee, Jaiwoo Lee, Yu-Kyoung Oh.

  Mitochondrial transplantation has emerged as a promising therapeutic strategy for neurological diseases associated with mitochondrial dysfunction. However, its application to central nervous system (CNS) disorders remains limited by the restrictive nature of the blood-brain barrier (BBB). Here, we report neutrophil-like mitochondria (nePM@Mito), engineered by coating isolated mitochondria with neutrophil plasma membranes to facilitate CNS delivery. By presenting neutrophil-derived surface adhesion molecules, nePM@Mito interact with endothelial receptors and recapitulate key features of neutrophil transendothelial migration, facilitating BBB crossing via endothelial exocytosis. In a mouse model of Parkinson's disease, intravenous administration of nePM@Mito leads to pronounced CNS accumulation and attenuation of oxidative stress. Delivered mitochondria restore mitochondrial function and increase tyrosine hydroxylase expression in dopaminergic neurons of the substantia nigra, resulting in elevated dopamine levels and improved motor performance. Notably, neutrophil membrane functionalization endows mitochondria with CNS-homing capability while preserving their intrinsic biological activity. The neutrophil-like mitochondrial delivery strategy provides a versatile platform for overcoming BBB limitations and offers a promising therapeutic approach for neurodegenerative diseases involving mitochondrial dysfunction.

Keywords:  Parkinson’s disease; blood−brain barrier; mitochondrial transplantation; neuroprotection; neutrophil-like mitochondria

DOI:  https://doi.org/10.1021/acsnano.5c22296
Adv Exp Med Biol. 2026 ;1509 423-444

Nano- and Microtubes: Tiny Fusion Events but Not Overall Plasma Membrane Merger for Exchanging Intracellular Components.

Xianghe Qiao, Bo Li.

  Membrane nanotubes, including tunneling nanotubes (TNTs), tumor microtubes (TMs), cytonemes, and related structures, constitute open-ended conduits that directly connect cells. They enable the directed exchange of organelles, nucleic acids, proteins, and ions across tens to hundreds of micrometers while preserving cellular identities. Specifically, this chapter synthesizes the current understanding of mechanisms, delineates cargo selectivity and transfer modes, and integrates cancer-relevant functions, such as mitochondrial transfer, calcium-wave propagation, and therapy adaptation. We emphasize rigorous criteria and multimodal workflows to distinguish conduit-mediated exchange from gap junction coupling, extracellular vesicles (EVs), trogocytosis, entosis, and bona fide cell-cell fusion. Across carcinomas and malignancies, tubes organize multicellular networks that distribute stress, shape metabolic plasticity, and seed resistant subclones. We outline vulnerabilities in tube biogenesis and coupling, propose a communication-fusion continuum, and set near-term priorities for in vivo quantification and translational targeting.

Keywords:  Intercellular cargo transfer; Mitochondria transfer; Non-fusogenic cell–cell communication; Tumor microtubes (TMs); Tunneling nanotubes (TNTs)

DOI:  https://doi.org/10.1007/978-3-032-22637-2_16
Bioact Mater. 2026 Sep;63 975-997

Mitochondrial micro-nano reactors via enhancing mitochondrial transfer and mitophagy for alleviating metabolic crisis.

Jiayi Mao, Wenzheng Xia, Minxiong Li, Xin Huang, Yun Zhao, Zheyuan Hu, Yinghong Su, Juan Wang, Wenguo Cui, Tao Zan.

  Energy metabolic dysfunction is a major cause of impaired chronic wounds healing, in which disrupted mitochondrial transfer and autophagy imbalance further aggravate the cellular energy crisis. In this study, single-cell RNA sequencing (scRNA-seq) of clinical diabetic wound samples first identified a pivotal role for macrophage-to-fibroblast mitochondrial transfer in wound healing. This finding was further validated using diabetic wound models and histological analyses, highlighting these processes as potential therapeutic targets for alleviating energy metabolic stress. Based on these findings, we innovatively developed a mitochondrial micro-nano reactor (MtNR) that alleviates the energy metabolic crisis by concurrently enhancing mitochondrial transfer and autophagy. First, hypoxic-preconditioning combined with gene-edited techniques was used to generate M2 macrophage-derived mitochondria-trained apoptotic bodies (mABs). Subsequently, mABs were conjugated with piezoelectric short fibers (PSFS) via copper-free strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry to self-assemble into MtNR. This system promotes intercellular mitochondrial transport through the Miro1-mitochondria-dynein-microtubule complex. It also generates bionic electrical signals via mechano-electrical conversion, thereby restoring Pink1-Parkin-P62/SQSTM1-LC3-mediated mitophagy and mitochondrial homeostasis. In a diabetic mouse wound model, MtNR restored mitochondrial morphology, enhanced cellular energy biogenesis, reduced p62 accumulation, increased LC3 expression, and significantly promoted tissue repair, providing a promising therapeutic strategy for addressing the energy deficit in diabetic wounds.

Keywords:  Apoptotic bodies; Energy metabolism; Mitochondrial transfer; Mitophagy; Piezoelectricity

DOI:  https://doi.org/10.1016/j.bioactmat.2026.03.048
J Physiol Biochem. 2026 May 21. pii: 53. [Epub ahead of print]82(1):

The progress of mitochondrial function and transfer in stem cell regulation and therapy.

Yubing Zhang, Zhuojian Qu, Zhiliang Guo, Lijuan Zhang, Hong Li, Xiaoyun Zhang, Xiumei Guan, Xiaodong Cui, Wenxu Wang, Min Cheng.

  Mitochondria, serving as central organelles for energy metabolism, play a critical regulatory role in stem cell self-renewal and differentiation-a function increasingly supported by accumulating evidence and closely linked to various aging-related diseases. Central to their function in stem cell pluripotency are several key mechanisms, such as the control of reactive oxygen species, mitophagy, and mitochondrial-endoplasmic reticulum communication. Mitochondrial transfer, as an emerging intercellular communication mechanism, can enhance stem cell pluripotency and function by replacing damaged mitochondria or activating mitophagy in recipient cells. However, different transfer mechanisms can induce distinct effects on recipient cells. The development of artificial mitochondrial transfer technology, compared to traditional cell transplantation, reduces immune rejection and offers new strategies for stem cell therapy. This review examines the interplay between mitochondrial function and stem cell fate determination, discusses the therapeutic potential of mitochondrial transfer in stem cell-based regenerative strategies, and establishes a theoretical framework for understanding and treating mitochondrial dysfunctions and aging-associated pathologies.

Keywords:  Mitochondrial function; Mitochondrial transfer; Mitophagy; Reactive oxygen species; Stem cell regulation

DOI:  https://doi.org/10.1007/s13105-026-01192-0
Front Physiol. 2026 ;17 1721230

Mitochondrial metabolic reprogramming, quality control, and intercellular transfer in regulating macrophage plasticity.

Guanheng He, Qian Sun.

  Macrophage functional plasticity is intrinsically linked to metabolic reprogramming, including mitochondrial function, substrate utilization, and redox signaling. In response to hypoxia, infection, or tissue injury, macrophages rely on mitochondria not only for energy provision but, critically, for metabolic intermediates and reactive oxygen species (ROS) that serve as signaling molecules to guide gene expression reprogramming. While macrophage activation exists along a continuous spectrum, this review summarizes the distinct metabolic paradigms characterizing the classical M1-like (glycolysis-dominant) and M2-like (oxidative phosphorylation, OXPHOS-dominant) extremes, highlighting the molecular mechanisms where metabolic events-specifically tricarboxylic acid (TCA) cycle truncation and succinate accumulation-drive inflammatory polarization. Furthermore, we discuss the role of mitochondrial quality control, particularly dynamics and mitophagy, in maintaining macrophage homeostasis. Notably, recent evidence identifies "intercellular mitochondrial transfer" as a novel mode of immune microenvironment regulation, enabling damaged macrophages to restore function by acquiring exogenous mitochondria. A deeper understanding of these mechanisms offers new intervention targets for metabolic immunotherapy in sepsis, cancer, and chronic inflammatory diseases. Importantly, we emphasize that many of these metabolic and mitochondrial regulatory mechanisms are highly context-dependent, varying significantly across different tissues and disease microenvironments.

Keywords:  intercellular mitochondrial transfer; macrophage polarization; metabolic reprogramming; mitochondria; mitophagy

DOI:  https://doi.org/10.3389/fphys.2026.1721230
Adv Sci (Weinh). 2026 May 22. e75806

Xenogeneic Mitochondrial Transplantation Improves Selected Age-Associated Phenotypes in Mice.

Wenpeng Li, Xijia Wang, Yaning Hu, Zhen Yang, Tian Niu, Xingbo Zhao.

  Xenogeneic mitochondrial transplantation (xeno-MT) improves selected age-associated phenotypes and mitochondrial functional readouts in mice while engaging host mitochondrial quality-control-related pathways. Donor mitochondrial preparations with impaired membrane potential retained measurable activity, but both respiratory competence and in vivo efficacy declined progressively with more extensive room-temperature damage and were largely lost after complete disruption. Although beneficial effects were observed in additional donor contexts, the present study provides the most detailed in vivo evidence for yak-derived xeno-MT, and broader donor equivalence remains to be established. These findings support xeno-MT as proof-of-concept evidence of biological activity and short-term tolerability under the conditions tested, while long-term safety, germline relevance, and pathway-specific dependence remain to be defined.

Keywords:  ageing; age‐related features; mitochondrial heteroplasmy; mitochondrial quality control; xenogeneic mitochondrial transplantation

DOI:  https://doi.org/10.1002/advs.75806
Barrier Immun. 2026 May 04.

Novel Organelle-Based Intracellular Immunity with Mechanistic and Therapeutic Implications.

Keman Xu, Shih-Yu Hung, Fatma Saaoud, Ying Shao, Yifan Lu, Juanjuan Liu, Bo Yuan, Haiyan Xiang, Hong Wang, Xiaofeng Yang.

Immunity has traditionally been viewed through the lens of extracellular pathogen recognition and intercellular immune communication. However, emerging evidence reveals that immune regulation extends deeply into the intracellular space, where organelles function and metabolism as active immune signaling platforms. In this review, we synthesize recent advances that redefine immunity as a multiscale system integrating extracellular, intercellular, and intracellular immune mechanisms. We first outline the functional modules of intracellular immune sensing and inflammatory signaling, including plasma membrane recognition, cytosolic surveillance, inflammasome activation, membrane execution, and secretome-mediated outputs. We then present a systematic framework of organelle-based platforms that regulate intracellular immunity and inflammation. Among these, mitochondria emerge as central immune organelles that coordinate metabolic reprogramming, danger/damage signal sensing, and inflammatory activation. Beyond their canonical role in bioenergetics, mitochondria engage in dynamic organelle crosstalk, transmit immune signals through soluble mediators, metabolites and contact sites, and participate in intercellular mitochondrial transfer. We classify mitochondrial immune signaling into three principal modes: indirect signaling via soluble mediators, direct organelle crosstalk at mitochondrial contact sites, and intercellular mitochondrial transfer, highlighting how these mechanisms integrate metabolism with immune regulation. Finally, we summarize current clinical and translational immunotherapies across multiple immune layers, spanning barrier immunity, innate immunity, adaptive immunity, and intracellular immunity. Collectively, this review provides a new conceptual and mechanistic framework for intracellular immune regulation and underscores emerging therapeutic opportunities arising from targeting organelle-based immune pathways.

DOI: https://doi.org/10.1002/dni2.70011
Biosystems. 2026 May 20. pii: S0303-2647(26)00128-0. [Epub ahead of print]265 105818

Stress-triggered cell elimination stabilizes resource-limited cell collectives: An agent-based model.

Bertan Korkmaz.

  Mitochondria, long regarded as the cell's "powerhouses", also serve as intracellular quality-control modules that promote the elimination of damaged or proliferatively dysregulated cells. Alongside their energetic benefits, mitochondrial apoptosis regulation may have helped shape the earliest steps toward stable multicellular organization. An agent-based modeling framework is developed to isolate and quantify the evolutionary impact of a mitochondrial death-surveillance system under nutrient stress, independently of its energetic contribution. The model tracks two cell types - normal prokaryotic cells (NPCs) and dysfunctional prokaryotic cells (DPCs) - each characterized by three dynamic state variables: damage load, proliferation drive and energy deficit. Mitochondrial surveillance is formalized as a simplified rule that detects stress and eliminates dysfunctional cells when a critical dysregulation boundary is crossed. Across 1200 stochastic simulations spanning variable nutrient regimes and inoculum sizes, mitochondrial surveillance prolonged median colony-collapse time by approximately 17%-18% across both nutrient regimes. The results indicate that a mitochondria-linked, intrinsic apoptosis-like gate can stabilize simple microbial groups independently of bioenergetic benefit, and is consistent with the view that such quality-control mechanisms provided a selective advantage toward robust multicellular organization. The framework also provides a conceptual basis for viewing mitochondrial transplantation as a means to restore intracellular fate-decision control, rather than solely to augment energy supply, in settings such as aging and cancer.

Keywords:  Agent-based modeling; Apoptosis; Endosymbiosis; Mitochondria; Multicellularity

DOI:  https://doi.org/10.1016/j.biosystems.2026.105818