Mitochondria, the organelles found in most animal, plant, and fungal cells, are derived from ancient bacterial endosymbionts. They continue to maintain unique genes that play vital roles, such as producing ATP, the primary energy currency of the cell. Mitochondria also participate in various essential functions, including cell signaling, detection of viruses and bacteria, cell division, apoptosis (programmed cell death), and both innate and adaptive immune responses. Consequently, problems with mitochondrial function can lead to aging and diseases related to age.
Mitochondria are organelles present in the cells of animals, plants, and fungi. Descended from ancient bacterial endosymbionts, they retain specific genes, enabling them to generate ATP, which serves as chemical energy. Additionally, they play crucial roles in various processes, including cellular signaling, sensing pathogens, dividing, dying, and managing immune responses. Therefore, any dysfunction in mitochondria can lead to aging signs and age-related illnesses.
A notable research area focuses on the evolutionary transfer of mitochondria between cells. However, researchers have faced challenges due to a lack of clear and standardized terms and practices to articulate these transfers. Without a common vocabulary, different scientists might describe the same phenomenon differently, or use identical terms to refer to different processes.
“In recent years, we’ve learned that mitochondria can move from one cell to another, and isolated mitochondria can be transplanted similar to organ transplants,” stated Keshav K. Singh, Ph.D., a professor at the University of Alabama at Birmingham’s Department of Genetics. “While the origins of mitochondrial transfer remain uncertain, it has been identified across a wide range of eukaryotic organisms, such as yeast, mollusks, fish, and rodents, as well as in human cells. We are only starting to grasp how changes in this transfer process are linked to disease development and how we can utilize mitochondrial transfer and transplantation to create innovative treatments.”
In 2024, Singh, along with Jonathan Brestoff, M.D., Ph.D., from Washington University School of Medicine, established an international consortium for mitochondria transfer and transplantation. They led a team of 31 global researchers to formulate shared recommendations aimed at enhancing this field through the establishment of unified terminology and descriptions for mitochondrial transfer and transplantation. Their consensus paper, titled “Recommendations for mitochondria transfer and transplantation nomenclature and characterization,” was published in Nature Metabolism.
The publication starts with a historical overview of the field, tracing early discoveries to recent advancements in mitochondrial transfer and the evolution of therapeutic strategies, which include cell engineering and clinical trials for children requiring extracorporeal membrane oxygenation.
It outlines the various types of mitochondrial transfer and transplantation, noting that when both the donating and receiving cell types are established in vivo, it constitutes a mitochondria transfer axis. The study examines methods for defining mitochondrial transfer through reporter proteins and dyes, techniques to facilitate transfer, and the subsequent fate of mitochondria post cell entry. The terminology is classified according to mechanisms into contact-dependent mitochondrial transfer, whereby the donor and recipient cells physically connect, and contact-independent mitochondrial transfer.
The recommendations also explore therapeutic methods for mitochondrial transplantation, which includes definitions of transplants, variations, longevity, levels of engagement, and diversity within transplants; cell engineering with extracellular mitochondria; and medications that influence mitochondrial transfer. It is noteworthy that extracellular mitochondria are prevalent in humans; for instance, a single unit of blood platelets can contain approximately 3 to 12 billion extracellular mitochondria, which are routinely and safely transfused in clinical settings.
In conclusion, the paper states, “This proposed nomenclature aims to eliminate confusion stemming from the variety of terms associated with similar processes or subsets of extracellular mitochondria as the field advances. We acknowledge that mitochondrial transfer and transplantation are vibrant research domains and anticipate that new insights may prompt updates to the suggested terminology.”
Singh has been passionate about mitochondrial research for many years. He was the founding editor-in-chief of the journal Mitochondrion and established the Society for Mitochondria Research and Medicine. In 2007 and 2009, his lab demonstrated that isolated mouse mitochondria could be transferred into human cells through co-incubation, establishing proof of concept for mitochondrial diffusion, and showed that xenotransplanted platelet mitochondria from a young African American woman with aggressive breast cancer were able to mimic the aggressiveness of breast cancer in mice. At the time, these discoveries did not receive the recognition they warranted, according to Singh.
