Work

Crosstalk between autophagy and ferroptosis in diabetes

Year: 2025

Type: article

Abstract: Diabetes is a multifactorial metabolic disease involving complex disruptions in cellular homeostasis and multiple forms of regulated cell death. Among them, the interaction between autophagy and ferroptosis has recently gained increasing attention. Autophagy is a catabolic process essential for degrading damaged organelles and misfolded proteins, thus preserving cellular integrity. Ferroptosis, on the other hand, is a newly identified, iron-dependent form of cell death characterized by excessive lipid peroxidation. Emerging evidence suggests that these two processes are intricately linked through shared regulatory pathways involving iron metabolism, lipid homeostasis, and the antioxidant system. Their crosstalk plays crucial roles in key diabetic pathologies, including pancreatic β-cell dysfunction, insulin resistance, and vascular complications. This review provides a comprehensive overview of the molecular mechanisms underlying autophagy-ferroptosis interactions in diabetes and highlights how their cooperative or antagonistic actions contribute to disease progression. Additionally, we discuss novel therapeutic strategies aimed at modulating this interplay, which may offer promising avenues for improving outcomes in diabetes and its complications. Further studies are needed to define precise molecular targets and facilitate clinical translation.

Source: Genes & Diseases

DOI: 10.1016/j.gendis.2025.101936