The crosstalk between autophagy and ferroptosis in pulmonary fibrosis.

Pulmonary fibrosis (PF) is a progressive lung disorder characterized by excessive deposition of extracellular matrix (ECM) in the alveoli, with irreversible fibrotic remodeling and destruction of alveolar structures. Clinically, PF is manifested by progressive dyspnea and a decline in lung function. These manifestations contribute to a poor prognosis and significantly diminish the quality of life of affected individuals. Current therapeutic options for PF remain limited, highlighting the urgent need to elucidate its molecular mechanisms in order to develop novel treatment strategies. Recent studies have revealed that autophagy and ferroptosis, two critical cell death pathways, engage in intricate crosstalk mechanisms that regulate the pathogenesis of PF. Autophagy maintains cellular homeostasis by mediating lysosome-dependent degradation, whereas ferroptosis is characterized by iron-dependent lipid peroxidation. The interplay between autophagy and ferroptosis plays a pivotal role in modulating fibrosis progression. However, the mechanistic interactions between autophagy and ferroptosis in PF remain poorly understood, particularly regarding their bidirectional crosstalk and their unique role in PF progression. This review aims to systematically synthesize the current understanding of autophagy-ferroptosis interactions in PF, thereby identifying potential therapeutic strategies and drug targets for PF treatment.