bims-mitrat 2026-07-05 papers

J Orthop Translat. 2026 Jul;59 101143

Therapeutic effect of mitochondrial transfer on bone tissue diseases: treatment strategy of mitochondrial transplantation and delivery technology.

Zuping Wu, Yuzhe Guan, Ruifeng Song, Peng Chen, Xinyi Fang, Qian Chen, Xiaoyan Chen.

Disruptions in bone tissue metabolic balance can lead to osteoporosis, osteoarthritis, rheumatoid arthritis, and bone tumors. This disruption typically manifests as reduced or abnormal bone mass, accompanied by pathological changes such as inflammation, fractures, and pain. Recent studies have revealed that mitochondrial dysfunction is prevalent in the aforementioned pathological processes, participating in the regulation of bone tissue cell function and intracellular immune function. Mitochondrial transfer, a newly discovered physiological phenomenon in recent years, can regulate mitochondrial function within recipient cells, thereby influencing metabolic activities, proliferation, differentiation, apoptosis, and immune function of various bone tissue cells. This article primarily reviews the regulatory effects of mitochondrial transfer associated with MSCs on various cells in bone and joint tissues. Given the role of mitochondrial transfer in regulating bone metabolism, we elucidate the application of mitochondrial transfer therapy in the treatment of osteoporosis, osteoarthritis, rheumatoid arthritis, and other bone tissue diseases. The Translational Potential of this Article: This review elaborates in detail on the therapeutic strategies provided by mitochondrial transplantation technology or targeted mitochondrial delivery systems for the treatment of bone tissue diseases, based on the occurrence of mitochondrial transfer in bone tissue tips and its therapeutic effects on related diseases such as OA, RA, osteoporosis.

Keywords: Extracellular vesicle (EVs); Mitochondrial transfer; Osteoarthritis (OA); Osteoporosis; Rheumatoid arthritis (RA); Tunneling nanotubes (TNTs)

DOI: https://doi.org/10.1016/j.jot.2026.101143

J Vis Exp. 2026 Jun 12.

Standardized Immunofluorescence Imaging of Tunneling Nanotubes and Mitochondrial Transfer Between Astrocytes and Neurons.

Xiaoyan Du, Yang Deng.

Mitochondria are essential organelles that regulate energy production, cellular signaling, and metabolic homeostasis in neural cells. Tunneling nanotubes (TNTs) are thin membranous structures that mediate long-distance intercellular communication and facilitate the transfer of cellular components, including mitochondria, between connected cells. Reliable visualization of TNTs and mitochondrial transfer requires careful sample handling because these structures are highly fragile and sensitive to fixation, washing, and imaging conditions. This protocol describes standardized procedures for the fixation, staining, and confocal imaging of TNTs in astrocytes and astrocyte-neuron coculture systems. The workflow includes membrane and cytoskeletal staining for TNT visualization, mitochondrial labeling for tracking mitochondrial localization, and immunofluorescence staining for Miro1 colocalization analysis. Critical steps for preserving TNT morphology, including gentle washing and light-protected handling, are emphasized throughout the procedure. The protocol also outlines imaging approaches for the characterization of TNTs and mitochondria in fixed-cell preparations. These methods provide a reproducible experimental framework for studying TNT formation and mitochondrial transfer between neural cells in vitro.

DOI: https://doi.org/10.3791/71670

Trends Cell Biol. 2026 Jun 29. pii: S0962-8924(26)00102-9. [Epub ahead of print]

Horizontal transfer of mitochondria in cancer: The physiology reborn in disease?

Gustavo Ayala, Simon Grelet.

Intercellular mitochondria transfer has emerged as a new form of cell-to-cell communication with profound consequences for cellular fate. A growing body of evidence defines mitochondria transfer between cells as a new pathological program in which cancer cells appropriate functional mitochondria from donor cells, thereby co-opting conserved physiological mechanisms of energy allocation to gain bioenergetic and phenotypic advantages. Our recent work demonstrates the prevalence of mitochondria transfer at the nerve-cancer interface, with neurons, though not exclusively, serving as a prominent source of the organelle. This suggests an unrecognized role of the nervous system in systemic energy redistribution and indicates that tumors may exploit this ancient, physiologically grounded mechanism to fuel progression and metastasis.

Keywords: cancer neurometabolism; kleptoplasmy; mitochondria transfer

DOI: https://doi.org/10.1016/j.tcb.2026.06.003

J Nanobiotechnology. 2026 Jul 01.

Restoration of macrophage mitochondrial dynamics and trafficking with enzymatic magnesium-manganese layered double hydroxide for osteoporotic therapy.

Wenwen Mao, Kehan Wang, Jingxian Mao, Zhuobin Xu, Chun Pan, Dandan Li, Tingting Liu, Hao Chen, Huihui Wang, Cheng Huang, Sihan Hu.

Macrophages play pivotal roles at the interface of immune regulation and bone metabolism and frequently exhibit a proinflammatory phenotype that contributes to the osteoporotic microenvironment. We found that dysfunctional macrophages in the osteoporotic niche transferred injured mitochondria to osteoblasts, which was associated with increased cellular senescence and impaired osteogenic function. This detrimental mitochondrial transfer was associated with abnormal accumulation of succinate dehydrogenase (SDH), contributing to maintenance of the proinflammatory phenotype and mitochondrial injury. On the basis of this mechanism, a folate (FA)-modified magnesium-manganese layered double hydroxide (MgMn-LDH) loaded with the SDH inhibitor dimethyl malonate (DMM) was designed to modulate proinflammatory macrophages. This system promoted BNIP3-LC3B-associated mitophagy, which was accompanied by improved mitochondrial quality control, mitochondrial dynamics and mitochondrial transfer capacity. The functional mitochondrial transfer from treated macrophages to neighboring osteoblasts was associated with enhanced osteogenic activity under osteoporotic conditions. Furthermore, MgMn-LDH/DMM@FA treatment significantly ameliorated bone loss and improved bone microarchitecture in ovariectomized mice. Collectively, these findings suggest that mitigating mitochondrial injury and enhancing functional mitochondrial transfer in proinflammatory macrophages may represent a promising strategy for alleviating osteoporosis. An enzyme-active MgMn-LDH-based delivery system provides a potential therapeutic platform for osteoporosis intervention.

Keywords: Enzyme-active layered double hydroxide; Macrophage; Mitochondrial homeostasis; Osteoporotic microenvironment; Succinate dehydrogenase

DOI: https://doi.org/10.1186/s12951-026-04761-z

Nihon Yakurigaku Zasshi. 2026 ;161(4): 216-221

[Is it possible to generate artificial mitochondrial genome?]

Ken-Ichi Wada.

The mitochondrial genome (mtDNA) is a circular DNA of approximately 16.5 kbp, present at several thousand copies per cell. Although mtDNA is extremely small compared with the nuclear genome, it is quite important for life system because it encodes components essential for ATP production through oxidative phosphorylation. Since mtDNA mutations are thought to be implicated in a wide range of diseases, gene therapies targeting mtDNA are expected to provide promising treatment options for such disorders; however, current methods allow only limited manipulation of mtDNA. In this article, our recent efforts toward establishing mtDNA writing, a technology that would enable unrestricted and precise manipulation of mtDNA, are introduced. We hypothesized that creation of specialized host cells that preferentially accept exogenous mtDNA would be the key to achieving mtDNA writing. We named such host cells "e-mt cells" and assumed that cells maintaining a deviated type of mtDNA in a homoplasmic state could function as e-mt cells. To create e-mt cells, we developed a novel mitochondrial transfer method using a microfluidic device. This microfluidic device allowed direct and non-invasive mitochondrial transfer between live single cells by fusing them through a micro aperture (microslit/microtunnel). Furthermore, we successfully demonstrated single-mitochondrion transfer as well as cybrid generation via mitochondrial transfer into ρ0 cells. These findings suggest that the microfluidic device has the potential to achieve homoplasmic mtDNA modification through mtDNA cloning and is therefore expected to contribute to the creation of e-mt cells.

DOI: https://doi.org/10.1254/fpj.25090