bims-mitrat 2026-10-18 papers

Korean Circ J. 2026 Jul 23.

Mitochondrial Transplantation: An Emerging Therapeutic Option for Cardiovascular Disease.

Suin Park, Jehee Jang, Young-Won Kim, Jae-Hong Ko, Sungguan Hong, Sung Hoon Lee, Kei Hayashida, Ki-Woon Kang.

Cardiovascular diseases (CVD) continue to impose the greatest global burden of death, and mitochondrial injury is increasingly recognized as a key pathological driver across ischemic heart disease, cardiac arrest, and heart failure. In this context, mitochondrial transplantation (MT) has gained attention as a promising therapeutic approach that directly addresses bioenergetic deficits by delivering functional mitochondria to compromised myocardium. This review examines current evidence for MT in CVD and evaluates its translational potential. We comprehensively reviewed preclinical studies and early clinical data on MT in CVD models, focusing on isolation techniques, delivery mechanisms, cellular uptake pathways, and therapeutic outcomes. Key databases were searched for relevant studies published through November 2025. MT demonstrates significant cardioprotective effects across diverse CVD models, including reduction in infarct size, restoration of adenosine triphosphate production, and improved functional recovery. Multiple cellular uptake mechanisms have been investigated, including actin-dependent endocytosis, macropinocytosis, and tunneling nanotubes. Advanced delivery strategies incorporating surface modifications, hydrogel platforms, and targeted peptides have improved mitochondrial stability and homing efficiency. Proposed mechanisms extend beyond bioenergetic rescue to include modulation of autophagy, oxidative stress reduction, and immunometabolic regulation. However, critical challenges remain regarding uptake efficiency, biodistribution, persistence, standardization protocols, and immunological considerations. MT represents a paradigm-shifting approach to cardiovascular therapeutics with encouraging preclinical results. Rigorous clinical trials with standardized methodologies are essential to establish safety, efficacy, and optimal implementation strategies for clinical translation.

Keywords: Cardiovascular disease; Mitochondria; Transplantation

DOI: https://doi.org/10.4070/kcj.2026.0074

Clin Transl Med. 2026 Oct;16(10): e70857

After delivery: How recipient cells shape the fate and function of transplanted mitochondria.

Zhi-Yuan Zhang, Bo-Quan Qin, Shi-Zhou Wu, Hui Zhang.

BACKGROUND: Mitochondrial transplantation is built on a simple idea: failing cells might be rescued by healthy mitochondria. The approach has entered early clinical testing, and encapsulation and cell-type targeting have improved uptake in selected systems. Better delivery, however, does not explain the therapy.
MAIN BODY: Internalised donor mitochondria encounter an established network, quality-control machinery and sensors for mitochondrial material. Donor material may remain in the endolysosomal system or reach the cytosol. Cytosolic fates include network integration, clearance and a candidate functional contribution without fusion. Intracellular processing may also generate bioactive cargo. These fates imply different mechanisms and evidence requirements. This Review examines how recipient cells shape the contribution of internalised mitochondria, while recognising extracellular routes to benefit. We distinguish direct transplantation evidence from mechanistic support drawn from endogenous mitochondrial biology and natural intercellular transfer. The required donor fate and duration depend on the therapeutic task. Transient rescue may rely on short-term donor function or productive processing in specific models; sustained support may depend on continued donor function, recipient adaptation or redosing. Durable mitochondrial DNA (mtDNA) correction requires donor-mtDNA retention and replication.
CONCLUSIONS: Linking these tasks to product design, safety assessment and clinical endpoints shifts the question from how many mitochondria enter cells to what they accomplish after arrival.
KEY POINTS: Recipient-cell handling shapes what transplanted mitochondria do after uptake. Uptake, structural integration and donor mitochondrial DNA retention require distinct evidence. Transient rescue, sustained support and durable mitochondrial DNA correction impose different requirements. Therapeutic goals should guide donor selection, product testing and clinical endpoints.

Keywords: endosomal escape; heteroplasmy; innate immunity; mitochondrial fusion; mitochondrial transplantation; mitophagy; translational medicine

DOI: https://doi.org/10.1002/ctm2.70857

Mitochondrion. 2026 Oct 12. pii: S1567-7249(26)00114-5. [Epub ahead of print]92 102224

Mitochondrial orchestration of melanoma: A nexus of metabolism, immunity, and therapeutic vulnerability.

Patrycja Kłos, Siarhei Dabravolski.

Despite therapeutic advances, melanoma remains a lethal malignancy characterised by profound therapeutic resistance. Emerging evidence positions the mitochondrion not as a subordinate organelle but as a central command centre orchestrating the key hallmarks of the disease. This review synthesises the profound dysregulation of the melanoma mitochondrial landscape, detailing the shift from a simple Warburg model to a nuanced understanding of metabolic plasticity, the critical role of organellar dynamics, and the dual function of reactive oxygen species (ROS) as both damaging agents and vital signalling molecules. We explore how this rewired state provides the bioenergetic and biosynthetic currency for proliferation and is essential for the arduous process of metastasis, a journey facilitated by novel mechanisms of intercellular mitochondrial transfer. Critically, the mitochondrion serves as the decisive battleground at the tumour-immune interface. While melanoma cells actively sabotage T-cell mitochondrial fitness to drive immune exhaustion, the metabolic state of the tumour's own mitochondria dictates its immunogenicity and susceptibility to immune attack. This deep mechanistic insight has unveiled a rich portfolio of therapeutic strategies, from direct bioenergetic inhibitors and mitochondria-targeted nanomedicines to innovative modalities such as photodynamic immunotherapy and mitochondrial transplantation, which offer powerful avenues to overcome therapy resistance. Finally, we discuss the burgeoning potential of mitochondrial features as prognostic and predictive biomarkers, arguing that a holistic, systems-level view is essential for paving the way towards a new era of personalised 'mito-oncology' to combat this devastating disease.

Keywords: Biomarkers; Cancer metabolism; Immunotherapy; Melanoma; Metastasis; Mitochondria; Therapy resistance

DOI: https://doi.org/10.1016/j.mito.2026.102224

J Ethnopharmacol. 2026 Oct 13. pii: S0378-8741(26)01364-4. [Epub ahead of print]374(Pt 2): 122509

Ligustilide enhances TNT-mediated mitochondrial transfer to accelerate the reactivation of TECs in sleep deprivation induced postpartum mouse.

Yaoying Shu, Xiaoyu Lai, Xie Xu, Senxu Lu, Bai Tao, Jianbo Huang, Jianli Gao.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (Oliv.) Diels (Danggui) has been widely used by puerperae in China for postpartum recovery for more than a thousand years. Its key active ingredient, ligustilide (LIG), has been documented to exert thymus-repairing effects; however, its role and underlying mechanisms in postpartum thymic regeneration impairment remain unclear.
AIM OF THE STUDY: During the puerperium, the acutely atrophied maternal thymus gradually returns to its non-pregnant state. However, frequent sleep deprivation (SD) resulting from neonatal breastfeeding often slows down the thymus recovery process. This study investigated the efficacy and underlying mechanism of LIG, an active ingredient of A. sinensis, against SD-induced thymic regeneration disorder (SDTRD) in postpartum mice.
MATERIALS AND METHODS: Postpartum SD was induced by automated disturbance; a progesterone-estrogen withdrawal (PE) model followed by a 7-day high-dose steroid treatment. LIG (1 mg/kg) was administered during regeneration. Thymic architecture (H&E), thymic epithelial cells (TECs) localization (immunofluorescence), and thymocyte subsets (flow cytometry) were quantified. Spleen sjTREC, thymic cytokines, and transcripts for mitochondrial biogenesis/function were measured by qPCR. TEM assessed mitochondrial ultrastructure. Dual-color mitochondrial tracing combined with a thymocytes-iTECs co-culture system and a bone-marrow-cell thymic homing assay mapped intercellular mitochondrial transfer. Tunneling nanotubes (TNTs) were disrupted with cytochalasin D; Rho-GTPase activation (including Cdc42) was evaluated.
RESULTS: Postpartum mice with SD showed damaged mitochondrial ultrastructure and reduced mitochondrial biogenesis in TECs, leading to TECs dysfunction and interruption of postpartum thymic regeneration. LIG significantly restored the abnormal spatial localization of TECs, improved the reticular framework of cortical TECs (cTECs), promoted thymocyte development, and increased output of CD4+ T-cells. Mechanistically, LIG may facilitate the formation of F-actin-dependent TNTs between thymocytes and TECs, mediating mitochondrial transfer from thymocytes to dysfunctional TECs. This process may rely on Rho GTPase signaling pathways (Cdc42 activation) to regulate F-actin polymerization.
CONCLUSIONS: LIG may promote F-actin-dependent TNT-mediated mitochondrial transfer from thymocytes to TECs, thereby reactivating TECs, restoring the thymic microenvironment, rescuing thymocyte development and export, and ultimately ameliorating SD-induced postpartum thymic regeneration. These findings provide new experimental evidence for developing LIG as a preventive and therapeutic intervention for defective postpartum thymic repair.

Keywords: Ligustilide; Mitochondrial transfer; Sleep deprivation; Tunneling nanotubes

DOI: https://doi.org/10.1016/j.jep.2026.122509