4.7 Article

Mitochondrial transplantation in cardiomyocytes: foundation, methods, and outcomes

Journal

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 321, Issue 3, Pages C489-C503

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00152.2021

Keywords

ischemia reperfusion injury; mitochondrial diseases; mitochondrial transplantation; mitochondrial transfer; mitochondrial cardiomyopathy

Funding

  1. National Science Foundation [2109959]
  2. Directorate For Engineering
  3. Div Of Chem, Bioeng, Env, & Transp Sys [2109959] Funding Source: National Science Foundation

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Mitochondrial transplantation is a novel cellular biotherapy that shows promise in alleviating mitochondrial damage and dysfunction, and potentially improving outcomes of various diseases related to mitochondrial function. By transferring mitochondria from different sources into cells, it has been shown to positively modulate bioenergetics and improve disease outcomes.
Mitochondrial transplantation is emerging as a novel cellular biotherapy to alleviate mitochondrial damage and dysfunction. Mitochondria play a crucial role in establishing cellular homeostasis and providing cell with the energy necessary to accomplish its function. Owing to its endosymbiotic origin, mitochondria share many features with their bacterial ancestors. Unlike the nuclear DNA, which is packaged into nucleosomes and protected from adverse environmental effects, mitochondrial DNA are more prone to harsh environmental effects, in particular that of the reactive oxygen species. Mitochondrial damage and dysfunction are implicated in many diseases ranging from metabolic diseases to cardiovascular and neurodegenerative diseases, among others. While it was once thought that transplantation of mitochondria would not be possible due to their semiautonomous nature and reliance on the nucleus, recent advances have shown that it is possible to transplant viable functional intact mitochondria from autologous, allogenic, and xenogeneic sources into different cell types. Moreover, current research suggests that the transplantation could positively modulate bioenergetics and improve disease outcome. Mitochondrial transplantation techniques and consequences of transplantation in cardiomyocytes are the theme of this review. We outline the different mitochondrial isolation and transfer techniques. Finally, we detail the consequences of mitochondrial transplantation in the cardiovascular system, more specifically in the context of cardiomyopathies and ischemia.

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