Ozone exposure and ferroptosis: Mechanistic links and current evidence.

Abstract

Ambient ozone (O₃) is a highly reactive secondary air pollutant whose health relevance is increasingly recognized. Although epidemiological evidence has linked O₃ exposure to multiple diseases, the biological mechanisms underlying the health effects remain incompletely understood. Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, has been implicated in diverse diseases and is increasingly considered a potential mechanism underlying pollutant-induced health injury. Notably, the core biochemical features of ferroptosis closely align with multiple O₃-induced molecular responses, including reactive oxygen species accumulation, excessive lipid peroxidation, and impaired antioxidant defenses, suggesting that ferroptosis may be a regulated cell death mechanism involved in O₃-related toxicity. However, evidence linking O₃ exposure to ferroptosis remains limited and fragmented. Therefore, this review synthesizes current mechanistic insights and available evidence connecting O₃ exposure with ferroptosis. Relevant literature was retrieved from databases including PubMed, Web of Science, and Scopus, covering studies published up to May 2026, and included studies addressing O₃ exposure in relation to ferroptosis, or to ferroptosis-relevant processes such as lipid peroxidation, antioxidant disruption, iron dyshomeostasis, or mitochondrial dysfunction. We further discuss current limitations and priorities for future research, with the aim of evaluating ferroptosis as a candidate mechanism underlying O₃-associated health effects.