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.
Highlights
As one of the most complex and important organelles within eukaryotic cells, mitochondria provide essential energy for cell activities
Various stress factors that induce mitochondrial damage could facilitate the formation of tunneling nanotubes (TNTs) and the subsequent transfer of mitochondria, but few studies have focused on the initiation mechanism and regulation of these membranous protrusions. p53 activation was reported as an important TNT-initiating factor in response to cellular stress.[119]
It would be lucrative to exploit the new insights into its mechanisms to selectively catalyze or interrupt this kind of mitochondrial communication for tissue revitalization and homeostasis as well as tumor suppression
Summary
Delin Liu[1,2], Youshui Gao[1,2,3], Jiao Liu[4], Yigang Huang[1,3], Junhui Yin[3], Yuyao Feng[5], Linjing Shi[6], Bruno P. Besides restoring stressed cells and damaged tissues due to mitochondrial dysfunction, the intercellular mitochondrial transfer occurs under physiological conditions. Under pathological conditions, the intercellular mitochondrial transfer appears to rescue tissue damage, which has been frequently reported in the central nervous system (CNS), cardiovascular system, and respiratory system, and to contribute to multifunctional cellular activity and thereby have an impact on tumor therapy resistance and inflammation regulation.
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