Abstract
Cardiomyocytes are highly oxygen-dependent cells, relying on oxygen-driven oxidative phosphorylation to maintain their function. During hypoxia, mitochondrial ATP production decreases, leading to calcium overload, acidosis, and oxidative stress, which collectively trigger myocardial injury. Ischemic heart disease, caused by coronary atherosclerosis, results in myocardial ischemia and hypoxia, leading to ischemia-reperfusion (I/R) injury. Early myocardial injury is attributed to ischemia and hypoxia, but even after thrombolytic therapy, interventional surgery, or coronary artery bypass grafting (CABG) restores local blood flow and oxygen supply, myocardial reperfusion injury (I/R) may still occur. Mitochondria, often referred to as the "powerhouses" of the cell, play a crucial role in cellular energy production. In the early stages of ischemia and hypoxia, mitochondrial dysfunction disrupts mitochondrial homeostasis, causing the accumulation of unfolded or misfolded proteins in the mitochondria. This activates the mitochondrial unfolded protein response (mtUPR) and mitophagy, which work to clear damaged proteins and mitochondria, playing a key role during this period. This review focuses on mitochondrial mechanisms during the ischemic phase of ischemia-reperfusion injury, aiming to provide new theoretical foundations and potential therapeutic strategies to reduce myocardial damage.