Mitochondrial ferroptosis in cardiovascular diseases: Mechanisms, biomarkers, and therapeutic opportunities — A narrative review

Background cardiovascular diseases (CVDs) are propelled by mitochondrial ferroptosis, an iron-dependent cell death involving ROS-driven lipid peroxidation, with mitochondria as key regulators via dynamics, iron flux, and antioxidant defences like GPX4/NRF2. Objectives To delineate mitochondrial mechanisms in ferroptosis across CVDs (I/R injury, heart failure, atherosclerosis), identify biomarkers (e.g., SUCLG1, mtDNA), evaluate therapies (Fer-1, MitoQ), and highlight translational gaps. Methods Narrative synthesis per PRISMA-ScR of PubMed/Scopus literature (Up to April 2026) on mitochondrial ferroptosis in CVD models, emphasizing proteomics, dynamics (Drp1/Mfn), and interventions.​ This narrative review was conducted to summarize the role of mitochondria in ferroptosis associated myocardial infarction. The databases searched were PubMed, Scopus, Google Scholar, ResearchGate, ScienceDirect, PubMed Central. The search included papers published until April 2026. The search terms used were “ferroptosis”, “mitochondria”, “Cardiomyocytes”, “Myocardial Infarction” “iron metabolism”, and “lipid peroxidation” with myocardial infarction, “Heart failure”, and Cardiovascular biomarkers. Results Mitochondria amplify ferroptosis through mitROS/cardiolipin oxidation, Fenton reactions, and impaired mitophagy; preclinical data show Fer-1/MitoQ reducing MI damage and plaque instability. Proteomic AMI markers (MDH2, HADHA) enable non-invasive detection. Conclusions Targeting mitochondrial ferroptosis offers precision CVD therapies, bridging oxidative stress/inflammation in atherosclerosis to clinical biomarkers and Nrf2/GPX4 modulation.