Intercellular mitochondrial transfer as a means of tissue revitalization

Abstract

As the crucial powerhouse for cell metabolism and tissue survival, the mitochondrion frequently undergoes morphological or positional changes when responding to various stresses and energy demands. In addition to intracellular changes, mitochondria can also be transferred intercellularly. Besides restoring stressed cells and damaged tissues due to mitochondrial dysfunction, the intercellular mitochondrial transfer also occurs under physiological conditions. In this review, the phenomenon of mitochondrial transfer is described according to its function under both physiological and pathological conditions, including tissue homeostasis, damaged tissue repair, tumor progression, and immunoregulation. Then, the mechanisms that contribute to this process are summarized, such as the trigger factors and transfer routes. Furthermore, various perspectives are explored to better understand the mysteries of cell–cell mitochondrial trafficking. In addition, potential therapeutic strategies for mitochondria-targeted application to rescue tissue damage and degeneration, as well as the inhibition of tumor progression, are discussed.

The Functions, Methods, and Mobility of Mitochondrial Transfer Between Cells

“…Naked mitochondria or mitochondrial components can also be extruded and internalized without carrier, which are also called exocytosis and endocytosis ( 5 ). Cytoplasmic vacuoles derived from plasma membrane engulf mitochondria and then fuse with cytomembrane to extrude the damaged mitochondria out under the condition of tumor necrosis factor-α (TNFα)-induced apoptosis in a actin and tubulin cytoskeletons-dependent manner ( 103 ).…”

“…Transcellular transfer of mitochondria facilitates the incorporation of the donated mitochondria into the endogenous network of recipient cells, which results the change in the bioenergetic profile and other functional properties of recipient cell (4). This process plays an important role in diverse pathological conditions, such as repair of tissue injury, inflammatory regulation, oncogenesis and tumor drug-resistance, as well as in physical conditions maintaining tissue homeostasis (5). Studies have shown that transcellular transfer of mitochondria involves multiple mechanisms, including formation of tunneling nanotubes (TNTs), extracellular vesicles (EVs), gap junctions, exocytosis and endocytosis of naked mitochondria, cytoplasmic fusion, and other metastasis modes (6)(7)(8).…”

“…Significantly, the most common donor cells in mitochondrial transcellular transfer are stem cells, such as WJMSCs, BMMSCs and iPSC-MSCs ( Table 1 ), which indicates that this process may play a crucial role in stem cell therapy ( 5 ). This type of cellular communication requires the transcellular transfer of mitochondria using all the methods mentioned above, among which tunneling nanotubes (TNTs) are the most common type of long-distance cellular connection.…”

Blood–Brain Barrier and Neurovascular Unit In Vitro Models for Studying Mitochondria-Driven Molecular Mechanisms of Neurodegeneration

“…Thus, we may assume that CD38 overexpression in astrocytes could serve as a mechanism to rescue affected neighboring cells with severe mitochondrial dysfunction (i.e., neurons in excitotoxic conditions, or cells in the epicenter of inflammation) by intercellular mitochondria transfer. Therefore, even usually CD38 effects in glial cells are thought to be linked to the control of intracellular NAD+ pool, new data on the role of CD38 in mediating the cell-to-cell transfer of donor mitochondria, expanding opportunities of utilizing intercellular communication for diminishing the neurological dysfunction [ 86 ].…”

Laterally transferred macrophage mitochondria act as a signaling source promoting cancer cell proliferation

“…Recent studies reveal that mitochondrial lateral transfer, the movement of mitochondria from one cell to another, can affect cellular and tissue homeostasis (1,2). Most of what we know about mitochondrial transfer stems from bulk cell studies and have led to the paradigm that functional transferred mitochondria restore bioenergetics and revitalize cellular functions to recipient cells with damaged or non-functional mitochondrial networks (3). However, mitochondrial transfer also occurs spontaneously between cells with functioning endogenous mitochondrial networks and enhances energy-consuming processes such as invasion and proliferation in the recipient cells.…”