One step forward: extracellular mitochondria transplantation.

Mitochondria play a key role in cellular energy production and contribute to cell metabolism, homeostasis, intracellular signalling and organelle's quality control, among other roles. Viable, respiratory-competent mitochondria exist also outside the cells. Such extracellular/exogenous mitochondria occur in the bloodstream, being released by platelets, activated monocytes and endothelial progenitor cells. In the nervous system, the cerebrospinal fluid contains mitochondria discharged by astrocytes. Various pathologies, including the cardiovascular and neurodegenerative diseases, are associated with mitochondrial dysfunction. A strategy to reverse dysfunction and restore cell normality is the transplantation of mitochondria (freshly isolated from a healthy tissue) into the zone at risk, such as the ischemic heart and/or damaged nervous tissue. The functional exogenous mitochondria will replace the harmed ones, ensuing cardioprotective and neuroprotective effects. The diversity of transplantation settings (in vitro, in animal models and patients) offered variable answers (including lack of consensus) on efficacy of this strategy. Therefore, a critical overview of the current and future trends in mitochondrial transplantation seems to be required. Here, we outline the recent developments on (i) extracellular mitochondria types and roles, (ii) transplantation protocols, (iii) mechanisms of mitochondrial incorporation, (iv) the benefit of extracellular mitochondria transplantation in human health and diseases and (v) open questions that deserve urgent answers.