Mechanisms of natural mitochondrial transfer in health and in cancer

This review discusses issues related to mitochondrial dynamics. It also highlights mechanisms allowing these organelles to transcend cell boundaries and transfer between mammalian cells. Mitochondria play a key role in energy generation and cellular physiological processes. These organelles are highly dynamic; they constantly change their morphology, cellular location, and distribution in response to cellular stress. In recent years, the phenomenon of mitochondrial transfer has attracted significant attention and interest from biologists and medical investigators. Intercellular mitochondrial transfer occurs in a different way, including tunneling nanotubes (TNTs), extracellular vesicles (EVS), and gap junction channels (GJCs). According to research on intercellular mitochondrial transfer in physiological and pathological environments, mitochondrial transfer has great potential for maintaining body homeostasis and regulating pathological processes. Recent evidence also suggests, that cell-free mitochondria release into blood under normal and pathological conditions (stress, trauma). They were found as circulating extracellular mitochondria in blood samples from mica and humans. Multiple research groups have developed artificial mitochondrial transfer/transplantation (AMT/T) methods that transfer healthy mitochondria into damaged cells and recover cellular function. This paper reviews intercellular spontaneous mitochondrial transfer modes, mechanisms, and the latest methods of AMT/T. Furthermore, potential application value and mechanism of AMT/T in disease treatment (including malignant neoplasms) are also discussed.