Horizontal mitochondrial transfer: New field of cell biology
Horizontal mitochondrial transfer (HMT) presents a phenomenon where mitochondria move between cells including mitochondrial DNA (mtDNA), in most cases with a functional impact for the cell that obtains mitochondria and, sometimes, also for the cell that loses these organelles. This phenomenon has been uncovered relatively recently, with first reports in the 90s of the last century.
HMT was initially described for in vitro systems, using co-culture of different cell types. One of the key pieces of evidence was coculture of mesenchymal stem cells (MSC) and lung cancer cells with depleted mtDNA. These so-called r0 cells do not have functional mitochondrial respiration, since mtDNA encodes 13 polypeptide, which are important for mitochondrial respirátory complexes. This involved transfer of mitochondria from MSC into r0 cells and to respiration normalization. A breakthrough came when the laboratory of Prof. Jiří Neužil together with the group of Prof. Michael Berridge (Malaghan Institute of Medical Research, Wellington, New Zealand) reported HMT in vivo in a mouse model of cancer and linked this phenomenon with the de novo pathway in cancer cells, important building units of DNA and RNA.
The phenomenon of HMT has since been studied in a variety of systems, such as mitochondrial transfer between platelets and MSC, facilitating wound healing, metween macrophages and T-cells supporting immune surveillence of cancer, or between supporting cells and osteocytes, which may promote later onset of osteoporosis. Recent research even showed that there is, wihtin normal physiology, constant transfer of mitochodnria between astrocytes and neurons, which could be utilized for suppresion of onset of neurodegenerative diseases, important in particular in the context of aging population.
Obviously, from relatively humble beginning linked to the discovery of HMT, this phenomenon has been documented for a range of pathologies and is also inherent to normal physiology and organ homeostasis. It is the dynamic development of HMT, which can now be considered as a new field of cell biology, which resulted in formation of a consortium of international experts, which now published in Nature Metabolism an important paper title „Recommendations for mitochondria transfer nomenclature and characterization“. It is expected that this publication will become a milestone in further development of therecently emerged discipline of HMT.
Further reading: https://www.nature.com/articles/s42255-024-01200-x
Author: prof. Jiří Neužil
