Autophagy and Ferroptosis—What Is the Connection?

Autophagy is a conserved intracellular degradation system and plays a dual role in cell death, depending on context and phase. Ferroptosis is a new form of regulated cell death that mainly depends on iron accumulation and lipid peroxidation. In this review, we summarize the processes of autophagy and ferroptosis and discuss their crosstalk mechanisms at the molecular level. The original study shows that ferroptosis is morphologically, biochemically, and genetically distinct from autophagy and other types of cell death. However, recent studies demonstrate that activation of ferroptosis is indeed dependent on the induction of autophagy. Additionally, many ferroptosis regulators such as SLC7A11, GPX4, NRF2, p53, HSPB1, CISD1, FANCD2, and ACSL4 have been identified as potential regulators of autophagy. This review not only highlights the importance of autophagy as an emerging mechanism of ferroptosis but also raises new insights regarding regulated cell death.