In this section
@article{Feng:2025:10.1007/s00408-025-00850-2,
author = {Feng, Y and Weng, J and Li, C and Liu, Q and Chang, Q and Zhang, H and Li, M and Wang, K and Wang, X and Chung, KF and Adcock, IM and Li, F},
doi = {10.1007/s00408-025-00850-2},
journal = {Lung},
title = {FUNDC1 promoted ferroptosis via JNK pathway in cigarette smoking-induced chronic obstructive pulmonary disease},
url = {http://dx.doi.org/10.1007/s00408-025-00850-2},
volume = {203},
year = {2025}
}
TY - JOUR
AB - BackgroundCigarette smoking (CS), the major risk factor for chronic obstructive pulmonary disease (COPD), induces oxidative stress, mitophagy, and ferroptosis. Because FUN14 domain-containing protein 1 (FUNDC1), a mitophagy receptor, may drive the onset and progression of COPD, we investigated its role in CS-induced ferroptosis in COPD and to explore the underlying cellular signaling mechanisms.MethodsWild-type (C57BL/6J background) and FUNDC1-knockdown (KD) mice were exposed to CS for 12 weeks. FUNDC1-KD and FUNDC1-overexpressing (OE) alveolar epithelial A549 cells were exposed to CS extracts (CSE) in the presence and absence of the JNK inhibitor, SP6001 (10 mM). Oxidative stress, inflammation, mitochondrial function, and ferroptosis were measured.ResultsFUNDC1 expression was increased in lung tissues from COPD patients and CS-exposed mice. CS exposure induced airway inflammation, reduced lung function, and enhanced ferroptosis in mice. FUNDC1-KD prevented CS-induced lung injury in mice. Similarly, CSE exposure up-regulated FUNDC1 expression, promoted ferroptosis, inflammation, oxidative stress, lipid peroxidation, and mitochondrial damage in A549 cells. FUNDC1-KD prevented CSE-induced cellular damage. Transcriptomic data indicated that FUNDC1 mediated ferroptosis through the JNK pathway. These in vitro results were further confirmed by pretreatment with the JNK inhibitor SP6001.ConclusionFUNDC1 plays an important role in CS-exposed alveolar epithelial cells and in a mouse model of COPD through the JNK-ferroptosis pathway.
AU - Feng,Y
AU - Weng,J
AU - Li,C
AU - Liu,Q
AU - Chang,Q
AU - Zhang,H
AU - Li,M
AU - Wang,K
AU - Wang,X
AU - Chung,KF
AU - Adcock,IM
AU - Li,F
DO - 10.1007/s00408-025-00850-2
PY - 2025///
SN - 0341-2040
TI - FUNDC1 promoted ferroptosis via JNK pathway in cigarette smoking-induced chronic obstructive pulmonary disease
T2 - Lung
UR - http://dx.doi.org/10.1007/s00408-025-00850-2
UR - https://doi.org/10.1007/s00408-025-00850-2
VL - 203
ER -