bims-mitrat 2025-07-13 papers

Cytotechnology. 2025 Aug;77(4): 139

Unlocking the potential of mitochondrial transplantation: overcoming challenges and paving the way for routine therapeutic application.

Amaneh Mohammadi Roushandeh, Kazuo Tomita, Yoshikazu Kuwahara, Nima Najafi-Ghalehlou, Tomoaki Sato, Mehryar Habibi Roudkenar.

Mitochondrial medicine has shown great promise as a therapeutic approach for treating currently incurable diseases. Preclinical studies highlight its safety and efficacy, but significant challenges remain in translating these therapies from bench to bedside. Key unresolved issues include understanding the mechanisms behind the reparative potential of transplanted mitochondria, such as their viability and functionality in an extracellular environment, especially under elevated calcium ion concentrations. Additionally, challenges related to mitochondrial sourcing, delivery methods, and ethical considerations need to be addressed for broader clinical adoption. This review analyses these challenges and explores strategies to overcome them, including refining mitochondrial sourcing, delivery techniques, and storage solutions. We also emphasise the need for rigorous ethical guidelines and regulatory frameworks to ensure safe and global implementation, paving the way for mitochondrial medicine's broader clinical use.

Keywords: Mitochondrial biology; Mitochondrial dysfunction; Mitochondrial medicine; Mitochondrial transplantation; Regenerative medicine

DOI: https://doi.org/10.1007/s10616-025-00805-8

J Heart Lung Transplant. 2025 Jul 05. pii: S1053-2498(25)02107-2. [Epub ahead of print]

Revitalizing Donor Organs: The Potential of Mitochondrial Transplantation in Heart and Lung Transplantation.

Aybuke Celik, Sandra Lindstedt, David C McGiffin, Jacky Y Suen, John F Fraser, Pedro J Del Nido, Sitaram M Emani, James D McCully.

Heart and lung transplantation remain the primary treatments for end-stage organ failure; yet organ shortages and ischemia-reperfusion injury (IRI) limit their success. Extended criteria donors (ECDs) have expanded the donor pool; however, prolonged cold ischemia times increase the risk of primary graft dysfunction (PGD). Static cold storage (SCS), the standard organ preservation method, is suboptimal, leading to mitochondrial dysfunction, ATP depletion, and oxidative stress. Recent advancements in organ storage show promise in maintaining graft viability. Mitochondria are key regulators of cellular homeostasis, and their dysfunction exacerbates IRI, contributing to inflammation and graft failure. Mitochondrial transplantation (MTx) has emerged as a novel therapeutic strategy to restore cellular bioenergetics, reduce oxidative stress, and improve graft function. Further research is needed to optimize MTx protocols and integrate them into current preservation techniques to enhance transplant success and long-term graft survival.

Keywords: heart transplantation; ischemia reperfusion injury; lung transplantation; mitochondria; mitochondrial transplantation; primary graft dysfunction

DOI: https://doi.org/10.1016/j.healun.2025.07.002

Biophys Physicobiol. 2025 ;22(2): e220012

A method for isolating and cryopreserving intact mitochondria with improved integrity and functionality.

Arima Okutani, Jannatul Naima, Asaka Ogihara, Taihei Motoichi, Ikuroh Ohsawa, Yoshihiro Ohta.

Mitochondria isolated from cells are essential tools in biological research. However, many mitochondria are often damaged during the isolation process. Although cryopreservation can greatly improve the usability of isolated mitochondria, it typically leads to significant loss of activity following freezing and thawing. In this study, we present our own techniques for mitochondrial isolation and cryopreservation to overcome these challenges. Our isolation method begins by selectively weakening the plasma membrane through the incorporation of digitonin, under conditions that do not increase membrane permeability. The plasma membrane is then selectively ruptured to release mitochondria. Notably, mitochondria contract within the cell before the plasma membrane ruptures, a process that facilitates their extraction. The isolated mitochondria showed polarized inner membranes in approximately 90% of the population. Compared to mitochondria isolated by homogenization, they retained more intermembrane space proteins and exhibited greater outer membrane integrity. For cryopreservation, rapid thawing was critical to maintaining mitochondrial activity after freeze-thaw cycles. When thawing was completed in under 1.5 minutes, the proportion of polarized mitochondria decreased by only about 10%. These findings suggest that our isolation and cryopreservation protocols are promising for applications requiring intact, functional mitochondria.

Keywords: cryopreservation; isolation; mitochondria

DOI: https://doi.org/10.2142/biophysico.bppb-v22.0012

Small Methods. 2025 Jul 06. e2500674

Mitochondrion in Pulmonary Disease: Small Organelle but Big Function.

Jiawen Wang, Honghui Wu, Jianqing Gao, Tianyuan Zhang.

Mitochondria are micrometer-sized organelles, yet are pivotal for the activity, function, and fate of mammalian cells. Recent findings further reveal that mitochondrial homeostasis plays an active role in regulating lung cell disorders, inspiring a novel strategy to treat pulmonary disease by restoring the imbalanced mitochondrial homeostasis. Pioneering studies have shown the potentials of this strategy for the treatment of pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS), which currently lack efficient medicines. However, there has been no comprehensive summary of this innovative strategy in pulmonary disease treatment. Therefore, the present review aims to provide an overview of the mechanism and advances in pulmonary disease treatment by restoring mitochondrial homeostasis. Particularly, some of the latest therapeutic strategies, including antioxidant therapy, mitochondrial quality controlling, and mitochondrial replenishment therapy (MRT), are introduced to show the potent capability of mitochondria to regulate cellular disorders in different types of lung cells. This review is believed to provide a general understanding of the mitochondria involved in pathogenesis and is intended to inspire the development of novel therapeutic methods against pulmonary diseases, focusing on regulating impaired mitochondrial homeostasis.

Keywords: antioxidants; homeostasis; mitochondria; mitochondria transfer; pulmonary diseases

DOI: https://doi.org/10.1002/smtd.202500674

Neural Regen Res. 2025 Jul 05.

Modulation of mitochondrial dysfunction: Mechanisms and strategies for the use of natural products to treat stroke.

Na Qin, Rujuan Liu, Rong Deng, Liuliu Shi, Lei Wang, Ting Zhu.

Modulations of mitochondrial dysfunction, which involve a series of dynamic processes such as mitochondrial biogenesis, mitochondrial fusion and fission, mitochondrial transport, mitochondrial autophagy, mitochondrial apoptosis, and oxidative stress, play an important role in the onset and progression of stroke. With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury, these modulations have emerged as a potential target for stroke prevention and treatment. Additionally, since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages, we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke. Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes: (1) Mitochondrial biogenesis: Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway, promote mitochondrial DNA replication and respiratory chain protein synthesis, and thereby restore energy supply in the ischemic penumbra. (2) Mitochondrial dynamics balance: Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue. (3) Mitochondrial autophagy: Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade, thereby alleviating blood-brain barrier damage. (4) Anti-apoptotic mechanisms: Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity, reducing neuronal programmed death induced by ischemia-reperfusion. (5) Oxidative stress regulation: Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway. (6) Intercellular mitochondrial transport: Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons. Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models. However, their clinical translation still faces challenges, such as the difficulty in standardization due to component complexity, insufficient cross-regional clinical data, and the lack of long-term safety evaluations. Future research should aim to integrate new technologies, such as single-cell sequencing and organoid models, to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials, providing theoretical support and translational pathways for the development of novel anti-stroke drugs.

Keywords: apoptosis; autophagy; hemorrhagic stroke; ischemic stroke; mitochondrial biogenesis; mitochondrial dynamics; mitochondrial dysfunction modulations; mitochondrial transport; natural products; oxidative stress

DOI: https://doi.org/10.4103/NRR.NRR-D-25-00016

Science. 2025 Jul 10. 389(6756): 157-162

ROS transfer at peroxisome-mitochondria contact regulates mitochondrial redox.

Maintenance of mitochondrial redox homeostasis is of fundamental importance to cellular health. Mitochondria harbor a host of intrinsic antioxidant defenses, but the contribution of extrinsic, nonmitochondrial antioxidant mechanisms is less well understood. We found a direct role for peroxisomes in maintaining mitochondrial redox homeostasis through contact-mediated reactive oxygen species (ROS) transfer. We found that ACBD5 and PTPIP51 form a contact between peroxisomes and mitochondria. The percentage of these contacts increased during mitochondrial oxidative stress and helped to maintain mitochondrial health through the transfer of mitochondrial ROS to the peroxisome lumen. Our findings reveal a multiorganelle layer of mitochondrial antioxidant defense-suggesting a direct mechanism by which peroxisomes contribute to mitochondrial health-and broaden the scope of known membrane contact site functions.

DOI: https://doi.org/10.1126/science.adn2804