Harnessing mitochondrial transplantation to sustain cardiac function: Another step forward

The mitochondria, apart from balancing optimal cellular homeostasis and energetics to sustain life, also mediate pathophysiological mechanisms leading to injury and death. In this regard, mitochondrial transplantation is emerging as a novel therapeutic strategy to circumvent deleterious effects of mitochondrial dysfunction in various pathological disorders. The transplantation of mitochondria involves the process of isolation, selection of optimal mitochondria, transfer, and internalization of exogenous intact mitochondria into the target cells or tissue. In the myocardium, metabolic and ionic changes secondary to the lack of oxygen are major contributors to mitochondrial damage. Mitochondrial transplantation has been demonstrated to protect against cardiac ischemia-reperfusion injury 1 Masuzawa A. Black K.M. Pacak C.A. Ericsson M. Barnett R.J. Drumm C. Seth P. Bloch D.B. Levitsky S. Cowan D.B. McCully J.D. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 2013; 304: H966-H982https://doi.org/10.1152/AJPHEART.00883.2012 Crossref PubMed Scopus (0) Google Scholar ,2 Cowan D.B. Yao R. Akurathi V. Snay E.R. Thedsanamoorthy J.K. Zurakowski D. Ericsson M. Friehs I. Wu Y. Levitsky S. et al. Intracoronary delivery of mitochondria to the ischemic heart for cardioprotection. PLOS One. 2016; 11: e0160889https://doi.org/10.1371/journal.pone.0160889 Crossref PubMed Scopus (140) Google Scholar ,3 Kaza A.K. Wamala I. Friehs I. Kuebler J.D. Rathod R.H. Berra I. Ericsson M. Yao R. Thedsanamoorthy J.K. Zurakowski D. et al. Myocardial rescue with autologous mitochondrial transplantation in a porcine model of ischemia/reperfusion. J. Thorac. Cardiovasc. Surg. 2017; 153: 934-943https://doi.org/10.1016/j.jtcvs.2016.10.077 Abstract Full Text Full Text PDF PubMed Scopus (131) Google Scholar ,4 Blitzer D. Guariento A. Doulamis I.P. Shin B. Moskowitzova K. Barbieri G.R. Orfany A. del Nido P.J. McCully J.D. Delayed transplantation of autologous mitochondria for cardioprotection in a porcine model. Ann. Thorac. Surg. 2020; 109: 711-719https://doi.org/10.1016/J.ATHORACSUR.2019.06.075 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar as well as to rescue the diabetic heart, 5 Doulamis I.P. Guariento A. Duignan T. Orfany A. Kido T. Zurakowski D. Del Nido P.J. McCully J.D. Mitochondrial transplantation for myocardial protection in diabetic hearts. Eur. J. Cardiothorac. Surg. 2020; 57: 836-845https://doi.org/10.1093/EJCTS/EZZ326 Crossref PubMed Scopus (0) Google Scholar with improved cardiac function and a reduction in infarct size.