Autophagy mediates an amplification loop during ferroptosis

Ferroptosis, a programmed cell death, has been identified and associated with cancer and various other diseases. Ferroptosis is defined as a reactive oxygen species (ROS)-dependent cell death related to iron accumulation and lipid peroxidation, which is different from apoptosis, necrosis, autophagy, and other forms of cell death. However, accumulating evidence has revealed a link between autophagy and ferroptosis at the molecular level and has suggested that autophagy is involved in regulating the accumulation of iron-dependent lipid peroxidation and ROS during ferroptosis. Understanding the roles and pathophysiological processes of autophagy during ferroptosis may provide effective strategies for the treatment of ferroptosis-related diseases. In this review, we summarize the current knowledge regarding the regulatory mechanisms underlying ferroptosis, including iron and lipid metabolism, and its association with the autophagy pathway. In addition, we discuss the contribution of autophagy to ferroptosis and elucidate the role of autophagy as a ferroptosis enhancer during ROS-dependent ferroptosis. [Image: see text]