Scientists Wrap Mitochondria in Protective Nanomaterials Without Halting Their Energy Production

Mitochondria are among the most fragile and most essential components of the living cell. Often described as cellular power plants, these tiny membrane-bound organelles convert nutrients and oxygen into adenosine triphosphate, the molecular currency that fuels virtually every energy-demanding process in the body. When mitochondria falter, the consequences can be devastating, particularly for tissues such as the brain and muscle that consume enormous quantities of energy. Now, a collaborative team from IRCCS Fondazione Istituto Neurologico Carlo Besta and Politecnico di Milano reports that it has achieved something once considered implausible: coating the outer surface of intact, functioning mitochondria with an engineered synthetic material, all without destroying the organelle’s ability to generate energy. The work, published in the Journal of the American Chemical Society, could open an entirely new avenue for treating mitochondrial dysfunction.

The material at the center of the study belongs to a family of compounds known as Metal-Organic Frameworks, or MOFs. These are crystalline structures built from metal ions or clusters connected by organic linker molecules, arranged in a repeating three-dimensional lattice. The result is a material with an extraordinarily high internal surface area and a modular architecture: by swapping the metal nodes or the organic linkers, chemists can tune the framework’s porosity, stability, reactivity, and interactions with biological systems. This design flexibility has made MOFs attractive for applications ranging from gas storage and separation to catalysis, sensing, and drug delivery. Their significance to chemistry was underscored in 2025, when the Nobel Prize in Chemistry was awarded to Susumu Kitagawa, Richard Robson, and Omar Yaghi for the development of these reticular materials.

Applying such materials to mitochondria, however, is far from straightforward. Mitochondria are delicate, double-membraned organelles whose function depends on the precise organization of protein complexes embedded in their inner membrane. Harsh chemical conditions, osmotic stress, or physical disruption can quickly collapse the membrane potential that drives energy production, rendering the organelles useless. Any coating strategy must therefore be gentle enough to preserve the structural integrity and bioenergetic activity of the mitochondria while still forming a stable layer on their outer surface. This tension between chemical modification and biological preservation is precisely the challenge the Milanese teams set out to solve.

The collaboration itself is a deliberate marriage of disciplines. It was conducted within the BraiNs joint laboratory, inaugurated in 2023, which brings together the mitochondrial biology expertise of the group led by Dr. Valeria Tiranti of the Medical Genetics and Neurogenetics Unit at Fondazione IRCCS Istituto Neurologico Carlo Besta, who also heads the Fondazione Mariani Centre for Paediatric Mitochondrial Diseases, and the chemical and materials engineering expertise of the group led by Professor Pierangelo Metrangolo at Politecnico di Milano. The pairing is apt: understanding what mitochondria need in order to survive manipulation is as important as knowing how to synthesize and functionalize a framework material around them.

The researchers developed a process that allows the surface of mitochondria to be coated directly with MOFs, using the materials in very small quantities. This minimization of dose is a key technical detail. At micromolar concentrations, as the study’s title indicates, the engineered frameworks interact with the organelles without overwhelming them or triggering the kind of chemical stress that would compromise their membranes. The most important finding of the work is what happened after the coating was applied: the mitochondria retained their ability to produce energy. In other words, the bioenergetic machinery inside the wrapped organelles continued to operate, suggesting that the coating does not interfere with the transport processes and membrane functions on which ATP synthesis depends.

For the field of mitochondrial medicine, the implications are considerable. Mitochondrial diseases are a group of often rare genetic disorders caused by defects in the organelles’ energy-producing machinery, which can reside either in the cell’s nuclear DNA or in the small circular genome that mitochondria carry themselves. Because mitochondria supply power to every tissue, these diseases can affect multiple organ systems, but they tend to strike hardest at the brain, muscles, heart, and other high-energy tissues. Treatment options today remain limited, consisting largely of supportive care, symptom management, and attempts to slow disease progression rather than correct the underlying defect. Any technology that allows mitochondria to be safely modified, protected, or delivered to cells would therefore represent a meaningful addition to a sparse therapeutic toolbox.

One application that the researchers highlight, still at an experimental stage, is mitochondrial transplantation. The idea behind this strategy is conceptually simple: transfer healthy mitochondria into cells whose own organelles are not functioning properly, thereby supplementing or replacing the defective energy supply. The practical obstacles, however, are substantial. Mitochondria isolated from donor cells are fragile, and getting them to survive the transfer process and then integrate productively into recipient cells is difficult. A specifically designed coating could, in principle, act as a protective and functional shell during this journey, stabilizing the organelles outside their native environment and facilitating their interaction with the recipient cell once they arrive.

Professor Metrangolo emphasized that the ability to modify the coating opens new research prospects. In the future, it should be possible to develop MOFs with different characteristics depending on the objective, creating coatings capable of performing specific functions. Because the chemical composition of a Metal-Organic Framework can be engineered with great precision, a coating could be designed to carry targeting molecules, to release protective agents, to respond to particular biological signals, or to alter how the mitochondria interact with their surroundings. In this sense, the coated organelle becomes something closer to a programmable biological unit: a living power plant wrapped in a tunable synthetic shell whose properties can be adjusted for the task at hand.

Dr. Tiranti echoed this vision, noting that a specifically designed coating could in the future facilitate both the transfer of mitochondria and the interaction between the transplanted organelles and the cells that receive them. Yet the researchers are careful to stress that this prospect has not yet been demonstrated. Further studies will be needed to determine whether a MOF coating actually offers a tangible advantage in transplantation compared with uncoated mitochondria. The current work establishes feasibility and safety of the coating process itself; whether the approach translates into improved outcomes for cell models, and eventually for patients with mitochondrial disease, remains an open question that the team and others in the field will now pursue.

The research was carried out as part of the doctoral project of Marco D’Amato, funded by the Calabria HUB for Innovative and Advanced Research (Cal.Hub.Ria) through funding under the Italian Ministry of Health’s Health Operational Plan. That a proof-of-concept of this kind emerged from a PhD candidate’s project reflects the way targeted national funding can support interdisciplinary work at the interface of materials chemistry and biomedicine. For now, the study stands as a striking demonstration that two of chemistry’s most celebrated synthetic materials can be brought into intimate contact with one of biology’s most delicate structures without breaking it. If subsequent experiments confirm that these engineered shells can genuinely enhance mitochondrial survival, delivery, and function, the humble power plants of the cell may one day be rebuilt, wrapped, and transplanted with the same precision that chemists apply to any other molecular architecture.

Subject of Research: Coating mitochondria with metal-organic framework materials while preserving their energy-producing function

Article Title: Coating mitochondria without damaging them: research opens a possible avenue for addressing their dysfunction

Article References: Coating mitochondria without damaging them: research opens a possible avenue for addressing their dysfunction. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: mitochondria, metal-organic frameworks, MOF, mitochondrial diseases, mitochondrial transplantation, bioenergetics, nanomaterials, cell biology, materials chemistry, Nobel Prize in Chemistry, ATP production, neurogenetics