Fig. 3

The dual role of autophagy in hepatic IRI. Autophagy plays a dual role in HIRI: moderate autophagy facilitates the clearance of damaged organelles and mitigates oxidative stress, whereas excessive autophagy can exacerbate cellular damage, leading to adverse outcomes. During the ischemic phase, protective autophagy is activated via AMPK stimulation owing to reduced ATP and oxygen levels, which inhibits mTOR, promotes ULK1 activation, and initiates the formation of protective autophagosomes. In the reperfusion phase, increased ROS levels activate BNIP3, resulting in the dissociation of the Beclin-1/Bcl-2 complex and the release of Beclin-1, thereby promoting autophagosome formation and contributing to the clearance of damaged organelles and proteins. However, overactivation of autophagy can lead to the excessive degradation of organelles and proteins, potentially forming harmful autophagosomes and exacerbating cellular damage. Therefore, maintaining autophagic homeostasis is crucial for alleviating hepatic ischemia–reperfusion injury. (Created using Adobe Illustrator)