Data AHA_CDA.xlsx

Mitochondria are the foremost player in ischemia-reperfusion (I/R) injury, which is one of the major contributors to myocardial infarction. Although current therapeutic options provide symptomatic relief, they fail to restore cardiomyocyte function, which represents a key roadblock in the treatment of reperfusion injury. Therefore, the ability to target mitochondrial pathways will likely provide a means to restore cardiomyocyte function, resulting in an effective and enhanced efficacy treatment. Efficient mitochondrial matrix protein quality control (mPQC) by LONP1 is crucial for cardiac bioenergetics. We compared young adult mice with cardiomyocyte-specific (Lonp1CKO-HET) or whole-body (Lonp1GKO-HET) haploinsufficiency and evaluated mitochondrial dynamics, including mitophagy markers, biogenesis markers, and mitochondrial stress markers. Despite similar cardiac Lonp1 reductions, only Lonp1CKO-HET mice showed mild dysfunction with mitochondrial stress response activation, altered dynamics, reduced biogenesis, and Tfam upregulation. Lonp1GKO-HET hearts lacked these changes, suggesting systemic mPQC deficiency can protect the heart via inter-organ signaling, a potential therapeutic strategy.