Work

Parkin–ACSL4 axis in ferroptosis regulation: a narrative review on therapeutic insights from exercise in aging cardiomyocytes

Year: 2026

Type: review

Abstract: Ferroptosis, iron-dependent regulated cell death, drives age-related cardiac dysfunction. This review examines aerobic exercise modulation of ferroptosis in aging cardiomyocytes via Parkin-ACSL4 axis. Parkin promotes ACSL4 ubiquitination/degradation, reducing lipid peroxidation and ROS. Exercise activates PINK1/Parkin mitophagy and hepcidin, enhancing mitochondrial resilience and iron homeostasis. Despite promising preclinical evidence, molecular mechanisms remain unclear. Aerobic exercise offers non-pharmacological cardiac protection against ferroptosis in aging.

Source: npj Metabolic Health and Disease

DOI: 10.1038/s44324-025-00092-z

Authors: Negin Kordi, Behnam Bagherzadeh-Rahmani, Rezvan KheirAndish, Raheleh Rezaali, Brent R. Stockwell