Press & Media - World Mitochondria Society

Bridge Over Troubled Cells: Bone Marrow Stromal Cells Transfer Mitochondria to Boost T Cells

2024-12-16T17:59:09+01:00

In a recent research published in Signal Transduction and Targeted Therapy, Lars Fabian Prinz,and his team present an innovative approach to combat T cell exhaustion using a bone marrow stromal cell (BMSC)-based mitochondrial transfer platform. This technique could revolutionize adoptive T cell therapies for cancer patients by addressing mitochondrial dysfunction in T cells.

Intercellular Mitochondrial Transfer: BMSCs transfer functional mitochondria to CD8+ T cells via tunneling nanotubes (TNTs), enhancing T cell metabolic fitness.
Improved Anti-Tumor Activity: Transferred mitochondria significantly boosted T cell resistance to exhaustion and anti-tumor effectiveness, both in vitro and in vivo.
Enhanced Therapeutic Potential: Mitochondrial-enriched (Mito+) T cells exhibited increased proliferation, reduced apoptosis, and higher cytotoxicity in tumor environments.

The study demonstrated enhanced outcomes in mouse models of melanoma and leukemia, with Mito+ T cells showing improved tumor suppression and survival rates. Challenges remain, including optimizing transfer efficiencies and overcoming tumor microenvironment constraints. However, this discovery opens doors for both cell-based and systemic therapies to modulate mitochondrial transfer for cancer treatment.

Figure Description

a Building on mitochondrial transfer techniques described in the literature, Baldwin and colleagues introduce a method to fortify CD8+ T cells with mitochondria transferred through tunneling nanotubules from bone marrow stromal cells (BMSCs). b The transfer results in T cells being more resistant against exhaustion and having higher anti-tumor activity in-vitro and in-vivo. c This could be applied to improve adoptive T cell therapies to treat patients with cancer. (Created with BioRender.com)

Source: https://www.nature.com/articles/s41392-024-02079-6

Image Credits: Prinz, L.F., Ullrich, R.T. & Chmielewski, M.M. B Sig Transduct Target Ther (2024).

Pseudomonas Bacteria Disrupt Mitochondrial Energy Production to Evade Immunity

2024-12-04T17:57:21+01:00

A recent eLife study uncovers how Pseudomonas aeruginosa, a pathogen notorious for its antibiotic resistance, undermines immune defense by targeting macrophage mitochondria. Researchers led by Laurence Rahme and Arijit Chakraborty from Harvard University identified a bacterial compound, 2-aminoacetophenone (2-AA), which impairs macrophage energy production, weakening their ability to combat infections.

Macrophages exposed to 2-AA show reduced production of ATP, the cell’s energy currency, due to the disruption of oxidative phosphorylation—a key mitochondrial pathway. This results in a buildup of pyruvate, indicating that it cannot enter mitochondria to fuel energy production. In animal models, mice infected with Pseudomonas mutants lacking 2-AA maintained normal ATP levels and had improved bacterial clearance compared to those infected with wild-type bacteria.

These findings not only highlight 2-AA as a potential therapeutic target to bolster immune defenses against Pseudomonas but also suggest its potential application in treating autoimmune diseases, where suppressing overactive immune responses may be beneficial.

Further research is ongoing to develop and evaluate inhibitors targeting 2-AA synthesis, with the aim of creating novel therapies for Pseudomonas infections.

Source: https://www.the-scientist.com/pseudomonas-bacteria-escape-immunity-by-disrupting-energy-production-in-macrophages-72350

Mitochondrial Dysfunction Disrupts Gut Microbiome, Possible Trigger for Crohn's Disease

2024-11-25T18:12:11+01:00

A recent study led by Prof. Dr. Dirk Haller at the Technical University of Munich (TUM) uncovers a critical connection between mitochondrial dysfunction and Crohn's disease (CD). The research demonstrates that defective mitochondria cause intestinal epithelial damage, triggering significant changes in the gut microbiome—key factors in the onset of this chronic inflammatory condition.

Key Findings:

Mitochondrial dysfunction leads to tissue damage in the intestinal epithelium, mimicking Crohn's disease symptoms.
Disruptions in mitochondrial function result in alterations to the gut microbiome composition.
This marks the first demonstration of a causal link between mitochondrial health and gut inflammation.

Implications for Treatment: Current Crohn's disease therapies focus on symptom management, but these findings open the door to novel approaches that target mitochondrial repair, potentially offering more effective, long-term solutions for managing CD.

Source: EurekaAlert

© Photo Credits: Urbauer, Elisabeth et al. Cell Host & Microbe (2024)

Study Shows Decreased Mitochondrial Creatine Kinase Impairs Muscle Function Independently of Insulin in Type 2 Diabetes

2024-11-25T17:27:42+01:00

Published in Science Translational Medicine

Researchers from Karolinska Institutet have uncovered a key factor contributing to impaired muscle energy production in individuals with type 2 diabetes. The study reveals that people with type 2 diabetes have reduced levels of creatine kinase, a protein responsible for metabolizing and converting creatine in muscle cells. This deficiency hampers mitochondrial function—the "powerhouses" of cells—leading to decreased energy production and increased cellular stress.

Creatine, a compound naturally produced by the body and found in foods like meat and fish, is critical for muscle function. Although creatine supplementation is popular for enhancing exercise performance, elevated blood creatine levels have been linked to an increased risk of type 2 diabetes. This study demonstrates that the reduced levels of creatine kinase observed in people with type 2 diabetes lead to impaired creatine metabolism, explaining the accumulation of creatine in their bloodstream.

“Our findings suggest that impaired creatine metabolism is a consequence of type 2 diabetes rather than a cause,” says Professor Anna Krook from the Department of Physiology and Pharmacology at Karolinska Institutet, the study’s principal investigator.

Moreover, the study shows that reduced creatine kinase levels directly affect mitochondrial function, independent of creatine availability. This discovery highlights the multifaceted role of creatine kinase in cellular energy production.

“This is consistent with the poorer energy metabolism seen in people with type 2 diabetes,” adds Professor Krook. “In the future, regulating creatine kinase could be explored as a potential treatment strategy for metabolic diseases like obesity and diabetes.”

The next phase of research will focus on identifying the molecular mechanisms linking creatine kinase levels to mitochondrial function.

Source: https://www.eurekalert.org/news-releases/1060405

Mitochondria’s Secret Strategy: How Cells Survive Starvation

2024-11-18T16:36:50+01:00

Mitochondria, often called the “powerhouses” of cells, are responsible for producing energy and vital molecules that cells need to function. However, until now, scientists have puzzled over how mitochondria manage to sustain these processes when cells are starved of nutrients. Researchers have uncovered that in low-resource conditions, mitochondria adopt a surprising strategy: they divide into two specialized forms. One form focuses on energy production to keep the cell powered, while the other concentrates on creating essential building blocks needed for repair and growth. This division of labor allows cells to survive and adapt even in challenging environments.

This remarkable discovery may also shed light on how some cancers thrive in hostile conditions within the body. Certain cancer cells appear to use the same mitochondrial strategy to fuel their growth and survival when nutrients are scarce. By splitting their functions, mitochondria in these cancer cells ensure the production of energy and key cellular components, enabling tumors to persist and grow even in environments that should inhibit them. Understanding this process offers new insights into cancer resilience and could pave the way for innovative treatments targeting mitochondrial functions in cancer cells.

This breakthrough highlights the extraordinary adaptability of mitochondria, offering a deeper understanding of cellular survival and disease mechanisms.

Military Medicine and Mitochondria: A Strong Interest in Targeted Strategies and Therapeutics

2024-09-27T13:19:36+02:00

During the 15th Annual Meeting of the World Mitochondria Society (WMS), taking place in Berlin, Germany, groundbreaking research on mitochondria-targeted medicine in military settings will be highlighted. This research, particularly focused on Traumatic Brain Injury (TBI) and polytrauma, is of significant interest due to the high incidence of such injuries in combat, where multiple organs are affected by mechanical trauma, thermal injuries, or exposure to harmful agents such as chemical, biological, radiological, or nuclear materials.

Mitochondria-targeted medicine has emerged as a crucial area for military medicine, especially for addressing TBI. Research from the Walter Reed Army Institute of Research has emphasized the essential role of mitochondrial function in the acute phase following TBI. The research shows that TBI leads to bioenergetic failure and disruptions in calcium and redox balance, which are critical for recovery. The findings suggest that therapies aimed at restoring mitochondrial function may serve as an effective neuroprotective approach.

Moreover, the detection of mitochondria-specific markers in biofluids presents exciting opportunities for advancing diagnostics and therapeutics for TBI. These discoveries could lead to more accurate diagnoses and the development of personalized therapies that enhance recovery for military personnel.

"The potential to target mitochondrial function in TBI treatment opens new doors for more effective interventions, offering hope for improved outcomes for service members affected by combat injuries", said Dr. Jignesh Pandya, Director of Brain Trauma Bioenergetics, Metabolism & Neurotherapeutics Development and leading researcher on the project.

These findings, which underline the military's growing focus on mitochondria-centric therapeutic strategies, will be a focal point of discussion at the WMS Annual Meeting, attracting attention from the global scientific and medical community.

More about Dr. Pandya's talk at Targeting Mitochondria 2024.

About the World Mitochondria Society (WMS)

The World Mitochondria Society (WMS) is an international organization dedicated to advancing research on mitochondria and their role in health and disease. The society promotes global collaboration among scientists and medical professionals to accelerate breakthroughs in mitochondrial medicine, diagnostics, and therapies. The WMS Annual Meeting serves as a platform for presenting the latest scientific advancements and fostering dialogue on the future of mitochondrial research.

For more information on this research and its implications for military medicine, please contact the WMS (mitochondria[at]wms-site.com).

Speakers Line-up and other topics.

Abstracts to be presented

State of the Science Mitochondria Specific-Targets, Therapeutics and Biomarker Investigations following Traumatic Brain Injury in the US Military
Jignesh D. Pandya, Walter Reed Army Institute of Research, USA
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Variation in Mitochondrial Functions across Vital Organs and Brain Sub-Regions in a Swine Model: A Novel Reference Targets forTBI and Polytrauma
Anke H. Scultetus, Walter Reed Army Institute of Research, USA
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Enhancing T Cell Antitumor Activity through Mitochondrial Transfer

2024-09-18T17:21:12+02:00

A recent study led by Jeremy G. Baldwin introduced a novel strategy to enhance the metabolic fitness and antitumor efficacy of CD8+ T cells.

The research demonstrated that bone marrow stromal cells (BMSCs) transfer mitochondria to T cells through intercellular nanotube connections, significantly increasing T cell mitochondrial mass and respiration. This process, requiring Talin 2 on both donor and recipient cells, improves the metabolic function of T cells, enabling them to infiltrate tumors more effectively and show fewer signs of exhaustion.

By utilizing this intercellular mitochondrial transfer, the study offers a new approach to overcoming T cell exhaustion, a critical challenge in immunotherapy. This breakthrough in organelle medicine could lead to the development of next-generation cell therapies with enhanced efficacy against cancer.

The latest innovations in mitochondrial research and mitochondrial transfer, including findings like this, will be discussed at the 15th World Congress on Targeting Mitochondria, taking place from October 29-31, 2024, in Berlin, Germany.

Article DOI.

Image Credits: Graphical Abstract Baldwin, Jeremy G. et al. Cell (2024)

Mitochondria: Key Players in Autism Spectrum Disorder?

2024-09-06T09:34:00+02:00

Recent review from the Hebrew University of Jerusalem highlighted the multifaceted role of mitochondria in Autism Spectrum Disorder (ASD), suggesting that mitochondrial dysfunction may significantly contribute to the development and pathology of this neurodevelopmental disorder. Mitochondria, essential for producing the aerobic energy necessary for brain function, have been found to exhibit abnormalities in individuals with ASD, which could profoundly impact brain development and function.

The brain displays high mitochondrial content, particularly in the synapses (shown in the upper left part of the figure). Increased mitochondrial levels of ROS, NO, and RNS, ETC impairments leading to the breakdown of OXPHOS and ATP production, dysregulation of the mitochondrial Ca2+cycling, imbalance between mitochondrial dynamics and mitophagy, prolonged opening of the mPTP, and activation of various mitochondria-related programmed cell death pathways, all contribute to the synaptic dysfunction and ASD. OXPHOS complexes are shown on the upper semisphere of the mitochondrion: I, NADH dehydrogenase; II, succinate dehydrogenase; III, ubiquinone cytochrome c oxidoreductase; IV, cytochrome c, cytochrome oxidase; and V, ATP synthase. Complexes I-IV belong to ETC.

ASD is associated with a variety of mitochondrial abnormalities, including impaired respiratory function, disrupted calcium (Ca2+) cycling, altered production of reactive oxygen and nitrogen species (ROS/RNS), and issues with the opening of the mitochondrial permeability transition pore (mPTP). These dysfunctions can lead to the activation of various mechanisms of programmed cell death, an imbalance in mitochondrial fusion, fission, and autophagy processes, and disturbances in synaptogenesis and synaptic transmission,all of which affect brain development and may result in behavioral deficits.

The importance of mitochondria in ASD cannot be overstated. These organelles are crucial for numerous cellular functions and can be affected by different pathogenic factors, which may explain the similarity in behavioral phenotypes seen in ASD cases of varying origins. Synapses, along with mitochondria, are considered key players in the molecular mechanisms related to ASD. The convergence of various neurodevelopmental pathological processes on synapses may partly explain the behavioral similarities observed in individuals across the autism spectrum.

Interestingly, as the recent review discusses, synaptic abnormalities are closely tied to mitochondrial dysfunction in ASD, suggesting that mitochondria-associated synaptic disturbances could present robust therapeutic targets that have yet to be explored. Although there are still many unknowns in the mitochondria-related mechanisms of autism, understanding these “blank spots” could pave the way for novel and effective treatments for ASD. This is particularly significant given the increasing prevalence of ASD and the current lack of effective pharmacological treatments.

Read the full review.

Figure credits: Khaliulin, I., Hamoudi, W. & Amal, H. Mol Psychiatry (2024).

Join Targeting Mitochondria 2024 Congress this October in Berlin to learn more about the impact of mitochondrial dysfunction on neurological disporders and other conditions.

Speakers Lineup.

Mitochondrial DNA in Our Brains Could Be Shortening Lifespan, New Study Reveals

2024-08-27T12:02:38+02:00

Recent groundbreaking research reveals that mitochondria, the tiny powerhouses of our cells, frequently insert their DNA into the nucleus of brain cells. This surprising finding, led by scientists at Columbia University Irving Medical Center, suggests that these insertions may be harmful and could be linked to a shorter lifespan.

Mitochondria release segments of mitochondrial DNA that can travel through pores of the nucleus and integrate into a cell’s chromosomes (where the insertions are called NUMTs, for nuclear mitochochondrial segments). A new study has found that nuclear mitochondrial DNA insertion—once thought rare—happens in the human brain likely several times over during a person’s lifespan. Credit: Martin Picard laboratory at Columbia University Vagelos College of Physicians and Surgeons

Mitochondrial DNA and Its Insertion into Chromosomes

Mitochondria, which are descendants of ancient bacteria, contain their own DNA, separate from the DNA in the cell’s nucleus. These tiny organelles have long been known for their role in energy production, but recent studies show they can also send fragments of their DNA into the nucleus. Once there, this mitochondrial DNA can integrate into the chromosomes, where it may disrupt normal cellular functions.

Potential Impact on Lifespan

The study examined DNA from nearly 1,200 individuals and found that people with more mitochondrial DNA insertions in their brain cells tended to die earlier than those with fewer insertions. This finding suggests that the integration of mitochondrial DNA into nuclear DNA might play a role in aging and lifespan. Researchers discovered that these DNA insertions are particularly common in the brain’s prefrontal cortex, a region crucial for cognitive function.

The Role of Stress

Interestingly, the research also found that stress might accelerate this process. Experiments with cultured human cells showed that under stress, mitochondria were more likely to release DNA, which then integrated into the cell’s chromosomes at a much faster rate. This discovery adds a new dimension to our understanding of how stress can impact our health at the cellular level.

Broader Implications

This study opens up new avenues for research into how mitochondrial DNA affects not just energy production, but also how it may contribute to aging and disease. The findings suggest that mitochondrial DNA insertions could be a new factor in genome instability, influencing not only the health of brain cells but also potentially contributing to conditions like Alzheimer’s disease.

Read the full paper.

Join Targeting Mitochondria 2024 Congress this October in Berlin, where several international speakers will highlight recent research on mitochondrial dynamics and genome stability.

Speakers Lineup.

Advances in Mitochondrial Modulation: How Infrared Light is Changing Brain Injury Recovery

2024-08-22T13:22:03+02:00

A recent study has spotlighted the transformative role of near-infrared (NIR) light in improving mitochondrial dynamics and quality control, offering new hope for brain injury recovery following cardiac arrest. Dr. Maik Hüttemann, Wayne State University (USA) and active member of the WMS Scientific Board will join Targeting Mitochondria 2024 Congress in Berlin, where he will delve deeper into these findings and discuss the advances in infrared light treatment.

Brain injury remains a significant challenge following cardiac arrest, with mitochondrial dysfunction playing a pivotal role in exacerbating neurological damage. The study investigates how targeting mitochondrial dysfunction with near-infrared light (NIR) wavelengths can mitigate brain injury following cardiac arrest. By employing various models, including isolated porcine brain cytochrome c oxidase (COX), primary mouse neurons, and large animal models, the research provides new insights into NIR-induced mitochondrial modulation.

The research demonstrates that NIR treatment reduces COX activity in an intensity-dependent manner, achieving a controlled modulation of mitochondrial function. This approach results in a moderate reduction of enzyme activity without complete inhibition. Additionally, in neuronal cells, NIR therapy has been shown to decrease mitochondrial swelling and enhance mitophagy, indicating improved mitochondrial health and quality control.

Practical application of NIR therapy has also been investigated. In anesthetized pigs, NIR was found to penetrate deep into the brain with minimal tissue heating, making it a feasible noninvasive treatment option. Moreover, in a model of out-of-hospital cardiac arrest, NIR treatment applied during resuscitation resulted in significantly improved neurological outcomes and reduced brain injury.

The study concludes that NIR effectively modulates mitochondrial function, enhancing mitochondrial dynamics and quality control after ischemia/reperfusion. This noninvasive technique offers promising potential for improving neurological recovery in patients resuscitated from cardiac arrest.

Join Dr. Hüttemann at the Targeting Mitochondria 2024 Congress in Berlin to know more about these findings and explore the future of mitochondria and photomedicine.

Article DOI.

Image credits: Wider, J.M., Gruley, E., Morse, P.T. et al. Modulation of mitochondrial function with near-infrared light reduces brain injury in a translational model of cardiac arrest. Crit Care27, 491 (2023).