bims-mitrat 2024-03-17 papers

bims-mitrat

Biomed News

on Mitochondrial Transplantation and Transfer

Issue of 2024‒03‒17
nine papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute

Mitochondria in the Central Nervous System in Health and Disease: The Puzzle of the Therapeutic Potential of Mitochondrial Transplantation.
The movement of mitochondria in breast cancer: internal motility and intercellular transfer of mitochondria.
Editorial: Advances and methods in mesenchymal stem cells.
Mitochondrial Dysfunction and Metabolic Reprogramming in Obesity and Asthma.
Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury.
Tunneling nanotubes and tumor microtubes-Emerging data on their roles in intercellular communication and pathophysiology: Summary of an International FASEB Catalyst Conference October 2023.
Transplanted human photoreceptors transfer cytoplasmic material but not to the recipient mouse retina.
Role of mitochondria in doxorubicin-mediated cardiotoxicity: from molecular mechanisms to therapeutic strategies.
Revisiting the Mitochondrial Function and Communication in Neurodegenerative Diseases.

Cells. 2024 Feb 27. pii: 410. [Epub ahead of print]13(5):

Mitochondria in the Central Nervous System in Health and Disease: The Puzzle of the Therapeutic Potential of Mitochondrial Transplantation.

Kuldeep Tripathi, Dorit Ben-Shachar.

  Mitochondria, the energy suppliers of the cells, play a central role in a variety of cellular processes essential for survival or leading to cell death. Consequently, mitochondrial dysfunction is implicated in numerous general and CNS disorders. The clinical manifestations of mitochondrial dysfunction include metabolic disorders, dysfunction of the immune system, tumorigenesis, and neuronal and behavioral abnormalities. In this review, we focus on the mitochondrial role in the CNS, which has unique characteristics and is therefore highly dependent on the mitochondria. First, we review the role of mitochondria in neuronal development, synaptogenesis, plasticity, and behavior as well as their adaptation to the intricate connections between the different cell types in the brain. Then, we review the sparse knowledge of the mechanisms of exogenous mitochondrial uptake and describe attempts to determine their half-life and transplantation long-term effects on neuronal sprouting, cellular proteome, and behavior. We further discuss the potential of mitochondrial transplantation to serve as a tool to study the causal link between mitochondria and neuronal activity and behavior. Next, we describe mitochondrial transplantation's therapeutic potential in various CNS disorders. Finally, we discuss the basic and reverse-translation challenges of this approach that currently hinder the clinical use of mitochondrial transplantation.

Keywords:  CNS; mitochondria; mitochondria and behavior; mitochondrial transplantation; neural development and function; neuropsychiatric disorders

DOI:  https://doi.org/10.3390/cells13050410
Clin Exp Metastasis. 2024 Mar 15.

The movement of mitochondria in breast cancer: internal motility and intercellular transfer of mitochondria.

Sarah Libring, Emily D Berestesky, Cynthia A Reinhart-King.

  As a major energy source for cells, mitochondria are involved in cell growth and proliferation, as well as migration, cell fate decisions, and many other aspects of cellular function. Once thought to be irreparably defective, mitochondrial function in cancer cells has found renewed interest, from suggested potential clinical biomarkers to mitochondria-targeting therapies. Here, we will focus on the effect of mitochondria movement on breast cancer progression. Mitochondria move both within the cell, such as to localize to areas of high energetic need, and between cells, where cells within the stroma have been shown to donate their mitochondria to breast cancer cells via multiple methods including tunneling nanotubes. The donation of mitochondria has been seen to increase the aggressiveness and chemoresistance of breast cancer cells, which has increased recent efforts to uncover the mechanisms of mitochondrial transfer. As metabolism and energetics are gaining attention as clinical targets, a better understanding of mitochondrial function and implications in cancer are required for developing effective, targeted therapeutics for cancer patients.

Keywords:  Breast cancer; Mitochondria; Mitochondrial transfer; Tunneling nanotubes; mtDNA

DOI:  https://doi.org/10.1007/s10585-024-10269-3
Front Cell Dev Biol. 2024 ;12 1382019

Editorial: Advances and methods in mesenchymal stem cells.

Pamela L Wenzel.



Keywords:  antioxidant activity; fibro-adipogenic progenitor cell; hematopoiesis; mesenchymal stem (stromal) cell; mitochondrial transfer; neural network models for morphology; neurotrauma and repair; vitiligo

DOI:  https://doi.org/10.3389/fcell.2024.1382019
Int J Mol Sci. 2024 Mar 03. pii: 2944. [Epub ahead of print]25(5):

Mitochondrial Dysfunction and Metabolic Reprogramming in Obesity and Asthma.

Paige Hartsoe, Fernando Holguin, Hong Wei Chu.

  Mitochondrial dysfunction and metabolic reprogramming have been extensively studied in many disorders ranging from cardiovascular to neurodegenerative disease. Obesity has previously been associated with mitochondrial fragmentation, dysregulated glycolysis, and oxidative phosphorylation, as well as increased reactive oxygen species production. Current treatments focus on reducing cellular stress to restore homeostasis through the use of antioxidants or alterations of mitochondrial dynamics. This review focuses on the role of mitochondrial dysfunction in obesity particularly for those suffering from asthma and examines mitochondrial transfer from mesenchymal stem cells to restore function as a potential therapy. Mitochondrial targeted therapy to restore healthy metabolism may provide a unique approach to alleviate dysregulation in individuals with this unique endotype.

Keywords:  asthma; inflammation; mesenchymal stem cells; metabolic reprogramming; mitochondrial dysfunction; obesity; reactive oxygen species

DOI:  https://doi.org/10.3390/ijms25052944
Exp Physiol. 2024 Mar 13.

Mitochondrial transplantation combined with coenzyme Q10 induces cardioprotection and mitochondrial improvement in aged male rats with reperfusion injury.

Soleyman Bafadam, Behnaz Mokhtari, Manoucheher Seyedi Vafaee, Zohreh Zavvari Oscuyi, Samira Nemati, Reza Badalzadeh.

  Ischaemic heart diseases (IHD) are among the major causes of mortality in the elderly population. Although timely reperfusion is a common treatment for IHD, it causes additional damage to the ischaemic myocardium known as ischaemia-reperfusion (IR) injury. Considering the importance of preventing reperfusion injuries, we aimed to examine the combination effect of mitochondrial transplantation (MT) and coenzyme Q10 (CoQ10 ) in myocardial IR injury of aged male rats. Seventy-two aged male Wistar rats were randomly divided into six groups: Sham, IR, CoQ10 , MT, combination therapy (MT + CoQ10 ) and vehicle. Myocardial IR injury was established by occlusion of the left anterior descending coronary artery followed by reopening. Young male Wistar rats were used as mitochondria donors. Isolated mitochondria were injected intraventricularly (500 µL of a respiration buffer containing 6 × 106 ± 5 × 105 mitochondria/mL) in MT-receiving groups at the onset of reperfusion. CoQ10 (10 mg/kg/day) was injected intraperitoneally for 2 weeks before IR induction. Twenty-four hours after reperfusion, haemodynamic parameters, myocardial infarct size (IS), lactate dehydrogenase (LDH) release and cardiac mitochondrial function (mitochondrial reactive oxygen species (ROS) generation and membrane potential) were measured. The combination of MT and CoQ10 improved haemodynamic index changes and reduced IS and LDH release (P < 0.05). It also decreased mitochondrial ROS generation and increased membrane potential (P < 0.05). CoQ10 also showed a significant cardioprotective effect. Combination therapy displayed greater cardioprotective effects than single treatments. This study revealed that MT and CoQ10 combination treatment can be considered as a promising cardioprotective strategy to reduce myocardial IR injury in ageing, in part by restoring mitochondrial function.

Keywords:  ageing; coenzyme Q10; mitochondrial transplantation; myocardial ischaemia/reperfusion injury

DOI:  https://doi.org/10.1113/EP091358
FASEB J. 2024 Mar 15. 38(5): e23514

Tunneling nanotubes and tumor microtubes-Emerging data on their roles in intercellular communication and pathophysiology: Summary of an International FASEB Catalyst Conference October 2023.

Emil Lou, Christel Vérollet, Frank Winkler, Chiara Zurzolo, Silvana Valdebenito-Silva, Eliseo Eugenin.

  In the past decade, there has been a steady rise in interest in studying novel cellular extensions and their potential roles in facilitating human diseases, including neurologic diseases, viral infectious diseases, cancer, and others. One of the exciting new aspects of this field is improved characterization and understanding of the functions and potential mechanisms of tunneling nanotubes (TNTs), which are actin-based filamentous protrusions that are structurally distinct from filopodia. TNTs form and connect cells at long distance and serve as direct conduits for intercellular communication in a wide range of cell types in vitro and in vivo. More researchers are entering this field and investigating the role of TNTs in mediating cancer cell invasion and drug resistance, cellular transfer of proteins, RNA or organelles, and intercellular spread of infectious agents, such as viruses, bacteria, and prions. Even further, the elucidation of highly functional membrane tubes called "tumor microtubes" (TMs) in incurable gliomas has further paved a new path for understanding how and why the tumor type is highly invasive at the cellular level and also resistant to standard therapies. Due to the wide-ranging and rapidly growing applicability of TNTs and TMs in pathophysiology across the spectrum of biology, it has become vital to bring researchers in the field together to discuss advances and the future of research in this important niche of protrusion biology.

Keywords:  cancer neuroscience; cellular protrusions; intercellular communication; protrusion biology; tumor microtubes; tunneling nanotubes

DOI:  https://doi.org/10.1096/fj.202302551
Stem Cell Res Ther. 2024 Mar 14. 15(1): 79

Transplanted human photoreceptors transfer cytoplasmic material but not to the recipient mouse retina.

Margaret T Ho, Kotoe Kawai, Dhana Abdo, Lacrimioara Comanita, Arturo Ortin-Martinez, Yui Ueno, Emily Tsao, Azam Rastgar-Moghadam, Chang Xue, Hong Cui, Valerie A Wallace, Molly S Shoichet.

  BACKGROUND: The discovery of material transfer between transplanted and host mouse photoreceptors has expanded the possibilities for utilizing transplanted photoreceptors as potential vehicles for delivering therapeutic cargo. However, previous research has not directly explored the capacity for human photoreceptors to engage in material transfer, as human photoreceptor transplantation has primarily been investigated in rodent models of late-stage retinal disease, which lack host photoreceptors.METHODS: In this study, we transplanted human stem-cell derived photoreceptors purified from human retinal organoids at different ontological ages (weeks 10, 14, or 20) into mouse models with intact photoreceptors and assessed transfer of human proteins and organelles to mouse photoreceptors.
RESULTS: Unexpectedly, regardless of donor age or mouse recipient background, human photoreceptors did not transfer material in the mouse retina, though a rare subset of donor cells (< 5%) integrated into the mouse photoreceptor cell layer. To investigate the possibility that a species barrier impeded transfer, we used a flow cytometric assay to examine material transfer in vitro. Interestingly, dissociated human photoreceptors transferred fluorescent protein with each other in vitro, yet no transfer was detected in co-cultures of human and mouse photoreceptors, suggesting that material transfer is species specific.
CONCLUSIONS: While xenograft models are not a tractable system to study material transfer of human photoreceptors, these findings demonstrate that human retinal organoid-derived photoreceptors are competent donors for material transfer and thus may be useful to treat retinal degenerative disease.

Keywords:  Human retinal organoids; Material transfer; Photoreceptor transplantation

DOI:  https://doi.org/10.1186/s13287-024-03679-3
Cell Stress Chaperones. 2024 Mar 12. pii: S1355-8145(24)00056-7. [Epub ahead of print]

Role of mitochondria in doxorubicin-mediated cardiotoxicity: from molecular mechanisms to therapeutic strategies.

Tianen Wang, Guoli Xing, Tong Fu, Yanchun Ma, Qi Wang, Shuxiang Zhang, Xing Chang, Ying Tong.

  This comprehensive review delves into the pivotal role of mitochondria in doxorubicin-induced cardiotoxicity, a significant complication limiting the clinical use of this potent anthracycline chemotherapeutic agent. Doxorubicin, while effective against various malignancies, is associated with dose-dependent cardiotoxicity, potentially leading to irreversible cardiac damage. The review meticulously dissects the molecular mechanisms underpinning this cardiotoxicity, particularly focusing on mitochondrial dysfunction, a central player in this adverse effect. Central to the discussion is the concept of mitochondrial quality control (MQC), including mitochondrial dynamics (fusion/fission balance) and mitophagy. The review presents evidence linking aberrations in these processes to cardiotoxicity in doxorubicin-treated patients. It elucidates how doxorubicin disrupts mitochondrial dynamics, leading to an imbalance between mitochondrial fission and fusion, and impairs mitophagy, culminating in the accumulation of dysfunctional mitochondria and subsequent cardiac cell damage. Furthermore, the review explores emerging therapeutic strategies targeting mitochondrial dysfunction. It highlights the potential of modulating mitochondrial dynamics and enhancing mitophagy to mitigate doxorubicin-induced cardiac damage. These strategies include pharmacological interventions with mitochondrial fission inhibitors, fusion promoters, and agents that modulate mitophagy. The review underscores the promising results from preclinical studies while advocating for more extensive clinical trials to validate these approaches in human patients. In conclusion, this review offers valuable insights into the intricate relationship between mitochondrial dysfunction and doxorubicin-mediated cardiotoxicity. It underscores the need for continued research into targeted mitochondrial therapies as a means to improve the cardiac safety profile of doxorubicin, thereby enhancing the overall treatment outcomes for cancer patients.

Keywords:  cardiotoxicity; doxorubicin; mitochondria; mitochondrial quality control

DOI:  https://doi.org/10.1016/j.cstres.2024.03.003
Curr Pharm Des. 2024 Mar 12.

Revisiting the Mitochondrial Function and Communication in Neurodegenerative Diseases.

Nitu L Wankhede, Mayur B Kale, Mohit D Umare, Sanket Lokhande, Aman B Upaganlawar, Pranay Wal, Brijesh G Taksande, Milind J Umekar, Prasanna Shama Khandige, Bhupendra Singh, Vandana Sadananda, Seema Ramniwas, Tapan Behl.

  Neurodegenerative disorders are distinguished by the progressive loss of anatomically or physiologically relevant neural systems. Atypical mitochondrial morphology and metabolic malfunction are found in many neurodegenerative disorders. Alteration in mitochondrial function can occur as a result of aberrant mitochondrial DNA, altered nuclear enzymes that interact with mitochondria actively or passively, or due to unexplained reasons. Mitochondria are intimately linked to the Endoplasmic reticulum (ER), and ER-mitochondrial communication governs several of the physiological functions and procedures that are disrupted in neurodegenerative disorders. Numerous researchers have associated these disorders with ER-mitochondrial interaction disturbance. In addition, aberrant mitochondrial DNA mutation and increased ROS production resulting in ionic imbalance and leading to functional and structural alterations in the brain as well as cellular damage may have an essential role in disease progression via mitochondrial malfunction. In this review, we explored the evidence highlighting the role of mitochondrial alterations in neurodegenerative pathways in most serious ailments, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD).

Keywords:  Alzheimer’s disease; Huntington’s disease; Neurodegenerative disorders; Parkinson’s disease; endoplasmic reticulum.; mitochondrial communication

DOI:  https://doi.org/10.2174/0113816128286655240304070740