Promotionsstipendien II/2020

Thema: " Studying the role of the mitochondrial electron transport chain in the rat heart challenged by ischemia-reperfusion (I/R) using alternative oxidase (AOX)"

Zusammenfassung:

Cardiovascular diseases (CVD) are a major socio-economic burden and leading cause of morbidity and mortality on a global scale. The etiology is most commonly based on ischemia-reperfusion (I/R) injuries attributed to stress signals arising from an impaired mitochondrial electron transport chain (ETC), which are specifically induced during the reperfusion phase. Mitochondrial stress signals include redox imbalance, metabolic stalling, ATP depletion and excessive production of reactive oxygen species (ROS). The latter are thought to specifically trigger cardiac contractile dysfunction. Alternative oxidase (AOX) is a respiratory enzyme, absent in mammals, that accepts electrons from a reduced quinone pool when the ETC is blocked thereby restoring electron flux and metabolism, and blunting ROS production. In principle, AOX may thus be considered a natural rescue mechanism from respiratory stress. Preliminary data from our lab, however, show contractile deterioration of the post-ischemic mouse AOX heart, thereby questioning current concepts. Using isolated, perfused rat hearts expressing AOX, this study aims to decipher the consequences of mitochondrial respiratory impairment and ROS production on cardiac metabolism and contractility.