bims-mitrat 2025-10-19 papers

Mol Biol Rep. 2025 Oct 17. 52(1): 1043

Breathing new life into male fertility: the potential of mitochondrial transplantation.

Bunty Sharma, Akshat Ashutosh Jha, Shafiul Haque, Hardeep Singh Tuli, Kawaljit Singh Kaura, Ujjawal Sharma.

Male infertility affects about 7% of men worldwide. Along with this disease also comes stigma and taboo that overshadow its emotional and psychological impacts. Despite its widespread prevalence, many cases of male infertility remain idiopathic. This review illustrates the use of mitochondrial transfer in addressing male fertility issues, particularly in situations where sperm movement is hindered and there are problems with mitochondrial function. Various factors can trigger male infertility, such as problems with sperm quality or quantity, genetic disorders, hormonal imbalances, testicular injuries, infections, or lifestyle habits. Stress, anxiety, and depression are parameters that can make matters worse by disrupting hormone levels and sperm production. Currently, there's no reliable treatment for mitochondrial dysfunction, which plays a role in oxidative stress and lower ATP production. Mitochondrial transfer works by injecting healthy mitochondria into deficient cells; this, in turn, improves ATP production and reduces oxidative stress. This leads to improvements in sperm motility and viability. The technique has already been used and found effective in improving embryo quality in human oocytes, which shows its potential application in male infertility treatments. Therefore, in the present review, we discussed the mechanisms used for mitochondrial transfer, intercellular communication pathways, purification, and delivery techniques that can enhance therapeutic outcomes. By consolidating recent advances in this domain, we aim to present a comprehensive overview of mitochondrial transfer as an innovative intervention in the management of male infertility. The ultimate goal is to transform male infertility from a challenging condition into a manageable one. This will offer new hope to affected individuals and couples through advanced reproductive technologies and targeted therapeutic interventions.

Keywords: Infertility; Male fertility; Mitochondrial transplantation; Sperm motility; Therapeutic application

DOI: https://doi.org/10.1007/s11033-025-11158-y

PLoS One. 2025 ;20(10): e0330322

Differential bioenergetic profile of human glioblastoma following transplantation of myocyte-derived mitochondria.

Kent L Marshall, Ethan Meadows, Alan Mizener, John M Hollander, Christopher P Cifarelli.

Glioblastoma (GBM) exhibits profound plasticity, enabling adaptation to fluctuating microenvironmental stressors such as hypoxia and nutrient deprivation. However, this metabolic rewiring also creates subtype-specific vulnerabilities that may be exploited therapeutically. Here, we investigate whether mitochondrial transplantation using non-neoplastic, human myocyte-derived mitochondria alters the metabolic architecture of GBM cells and modulates their response to ionizing radiation. Using a cell-penetrating peptide-mediated delivery system, we successfully introduced mitochondria into two mesenchymal-subtype GBM cell lines, U3035 and U3046. Transplanted cells exhibited enhanced mitochondrial polarization and respiratory function, particularly in the metabolically flexible U3035 line. Bioenergetic profiling revealed significant increases in basal respiration, spare respiratory capacity, and glycolytic reserve in U3035 cells post-transplantation, whereas U3046 cells showed minimal bioenergetic augmentation. Transcriptomic analyses using oxidative phosphorylation (OXPHOS) and glycolysis gene sets confirmed these functional findings. At baseline, U3035 cells expressed high levels of both glycolytic and OXPHOS genes, while U3046 cells were metabolically suppressed. Following radiation, U3035 cells downregulated key OXPHOS and glycolysis genes, suggesting metabolic collapse. In contrast, U3046 cells transcriptionally upregulated both pathways, indicating compensatory adaptation. These results identify and establish mitochondrial transplantation as a metabolic priming strategy that sensitizes adaptable GBM subtypes like U3035 to therapeutic stress by inducing bioenergetic overextension. Conversely, rigid subtypes like U3046 may require inhibition of post-radiation metabolic compensation for effective targeting. Our findings support a novel stratified approach to GBM treatment which integrates metabolic subtype profiling with bioenergetic modulation.

DOI: https://doi.org/10.1371/journal.pone.0330322

Naunyn Schmiedebergs Arch Pharmacol. 2025 Oct 17.

MUC1 promotes NSCLC progression by regulating ICAM-1-mediated mitochondria transfer from tCAFs to cancer cells.

Feifan Ji, Donglian Wang, Jingguang Jin, Jin Zhang, Lingyu Guan.

Cancer-associated fibroblasts (tCAFs) promote non-small cell lung cancer (NSCLC) progression through cargo exchange with cancer cells. Mucin 1 (MUC1) initiates actin-mediated cytoskeleton protrusion movement to promote mitochondrial transfer. In this study, we aimed to investigate whether MUC1 regulates mitochondrial transfer from tCAFs to NSCLC cells. The results showed that lung cancer patients with high MUC1 expression had a poor prognosis, and MUC1 protein was significantly enriched in exosomes (EXOs) derived from tCAFs. A549 cells were treated with conditioned medium (CM) or EXOs derived from tCAFs or co-cultured with tCAFs in contact or non-contact ways. Both CM and EXOs promoted the proliferation and invasion and inhibited apoptosis in A549 cells, while MUC1-interfered EXOs inhibited A549 cell proliferation and invasion and induced apoptosis. Meanwhile, non-contact co-culture of tCAFs and A549 cells promoted proliferation, invasion, and colony formation of A549 cells, and contact co-culture further promoted malignant phenotype of A549 cells and enhanced mitochondrial function in A549 cells. Mechanism studies revealed that MUC1 promotes mitochondrial transfer from tCAFs to A549 cells by interacting with intercellular adhesion molecule-1 (ICAM1), promoting malignant phenotype of A549 cells. ICAM1 interference counteracted the effect of EXO protein MUC1 on A549 cells. Finally, lung cancer xenograft tumor models were constructed and found that EXO protein MUC1 promoted lung cancer tumor growth in vivo, while ICAM1 interference inhibited tumor growth. In conclusion, MUC1 is enriched in EXOs derived from tCAFs and promotes NSCLC progression by regulating ICAM1-mediated mitochondria transfer from tCAFs to cancer cells.

Keywords: ICAM1; MUC1; Mitochondria transfer; NSCLC; TCAFs

DOI: https://doi.org/10.1007/s00210-025-04672-0

Front Aging. 2025 ;6 1688482

Nanoengineered mitochondria for mitochondrial dysfunction and anti-aging interventions.

Siqi Deng, Yingying Ren, Qian Zhang, Qinling Liu, Jiaxin Long, Kelsey Picard, Miguel Martin, Thomas Miller, Chaofan Yuan, Yunxiang He, Junling Guo.

Aging is a multifactorial process and a major risk factor for chronic disease. Among its hallmarks, mitochondrial dysfunction plays a central role, driven by impaired respiration and accumulated mitochondrial DNA mutations that disrupt energy metabolism and redox balance. Conventional mitochondrial transplantation has been explored as a therapeutic strategy, but its emphasis on increasing mitochondrial quantity without restoring function has limited success. Recent advances in nanoengineered mitochondria that integrate isolated mitochondria with functional nanomaterials, offer new opportunities to enhance organelle quality, boost metabolic activity, and achieve targeted delivery. Preclinical studies highlight their promise in cardiovascular, neurodegenerative, and other age-related disorders. In this mini-review, mitochondrial dysfunction in aging is first introduced, followed by the summary of rational designed strategies for engineering mitochondrial biohybrids and their emerging applications, and finally translational challenges are further discussed. By bridging materials science and mitochondrial therapy, nanoengineered mitochondria may represent a next-generation approach to anti-aging interventions.

Keywords: age-related diseases; anti-aging; mitochondrial function restoration; nanoengineered mitochondrial biohybrids; surface functionalization

DOI: https://doi.org/10.3389/fragi.2025.1688482