Ferroptosis in heatstroke: Mechanisms and therapeutic perspectives (Review).

Abstract

Heatstroke is a life‑threatening condition characterized by hyperthermia and systemic inflammatory response, often leading to multi‑organ dysfunction and high mortality. Despite advances in understanding its pathophysiology, effective targeted therapies remain limited. Recent studies have highlighted ferroptosis, an iron‑dependent, lipid peroxidation‑driven form of regulated cell death, as a critical mechanism in heatstroke‑induced organ injury. This review synthesizes current evidence on the role of ferroptosis in heatstroke, including key signaling pathways such as Hippo‑Yes‑associated protein‑acyl‑CoA synthetase long‑chain family member 4, dysregulated heat shock response, and antioxidant defense failure. The present study also explored potential ferroptosis‑related biomarkers and therapeutic strategies targeting this cell death pathway. Understanding ferroptosis in heatstroke not only unveils novel pathophysiological insights but also opens avenues for early diagnosis and targeted intervention.