Mitochondria Do Not Survive Calcium Overload During Transplantation

Abstract

utologous mitochondrial transplantation was recently proposed as a novel therapeutic strategy to restore cardiac function after myocardial infarction. he declared treatment goal is to replace mitochondria in cardiac myocytes damaged by ischemia with respiration-competent mitochondria, whose ATP formation supposedly sustains cardiac vitality and contraction. This approach was tested in preclinical models of ischemia/ reperfusion injury 1 and subsequently applied to pediatric patients with myocardial ischemia in an open-label, single-armed clinical trial (NCT02851758). We recently argued that the translation of this approach to the clinical arena may be premature, since it appears unlikely that injected mitochondria withstand high Ca 2+ concentrations in the extracellular environment. In response to our article, McCully et al, 1 who had introduced this approach, emphasized that "donor mitochondria are viable in both the isolated perfused heart, where Ca 2+ concentration was 1.7 mmol/L and in in vitro cell studies where Ca 2+ concentration was 1.8 mmol/L. " However, high extramitochondrial Na + concentrations in the bloodstream or extracellular fluid may potentially protect mitochondria from Ca 2+ overload by inducing Ca 2+ efflux via the mitochondrial Na + /Ca 2+ exchanger. To address this hypothesis, we isolated skeletal muscle mitochondria (as used in the studies by McCully et al) 1 from mice and

Topics & Concepts