Fig. 4

Deleterious effects of autophagy in MIRI. During ischemic conditions, cardiomyocytes shift to anaerobic metabolism, which leads to a reduction in ATP levels and an elevation in intracellular Na⁺ and Ca²⁺ concentrations. Upon reperfusion, there is an exacerbation of intracellular Ca²⁺ accumulation and ROS generation, culminating in MIRI. The principal apoptotic signaling pathways involved are the intrinsic pathway, mediated by mitochondrial mechanisms, and the extrinsic pathway, mediated by death receptors. During ischemia and the initial phase of reperfusion, cellular acidosis, disruption of homeostasis, and various other factors facilitate the enzymatic release of iron equivalents or iron ions. This process activates the Fenton reaction, resulting in elevated levels of ROS, ultimately inducing ferroptosis in cardiomyocytes. (Created using Adobe Illustrator)