Parkin–ACSL4 axis in ferroptosis regulation: a narrative review on therapeutic insights from exercise in aging cardiomyocytes
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.
Authors
- Rezvan Kheirandish
- Negin Kordi (ORCID: https://orcid.org/0000-0002-2586-1072)
- Brent R. Stockwell (ORCID: https://orcid.org/0000-0002-3532-3868)
- Behnam Bagherzadeh-Rahmani (ORCID: https://orcid.org/0000-0001-9900-0833)
- Raheleh Rezaali
Institutions
- Razi University (IR)
- Islamic Azad University Central Tehran Branch (IR)
- Technical and Vocational University (IR)
- Columbia University (US)
- Shomal University (IR)
Publication Details
- Journal
- npj Metabolic Health and Disease
- Published
- 2026-01-06
- DOI
- https://doi.org/10.1038/s44324-025-00092-z
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 0.00