Myocardial ischemia-reperfusion (IR) injury is a major clinical challenge in treating patients suffering from myocardial infarction (MI) as there is no effective therapy to date. In this work, we will employ new mouse models, cell culture, proteomics, molecular and cell biology techniques, and small molecule activators of LonP1 to study the mechanisms of LonP1 mediated cardioprotection in mitigating IR injury.
Our proposed work will delineate how LonP1 remodels Complex-I, its integrity, and activity during early IR, thereby reducing excess mtROS and preventing oxidative damage-induced cardiomyocyte death.