The ferroptosis inhibitor NUPR1 coordinates the mitochondrial response to oxidative stress and cell metabolism during COPD pathogenesis in the lung
7 affiliations
- 1Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.
- 2Department of Anesthesiology, Yale School of Medicine, New Haven, CT.
- 3Department of Cardiovascular and Thoracic Surgery, The First Affiliated Hospital of Chongqing Medical University.
- 4Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
- 5Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 163 Avenue de Luminy, 13288 Marseille, France.
- 6Division of Respirology, Department of Medicine, McMaster University School of Medicine, Ontario, CA.
- 7Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI.
Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by chronic injury and oxidative stress leading to progressive lung tissue destruction. Emerging evidence suggests that regulated cell death pathways, particularly ferroptosis, contribute to COPD pathology. We previously identified the stress response protein and known ferroptosis inhibitor nuclear protein 1 (NUPR1) as markedly downregulated in lung tissue from COPD patients. Here, we demonstrate that NUPR1 inhibition exacerbates iron accumulation, enhances lipid peroxidation, impairs mitochondrial function, disrupts cellular metabolism, and increases oxidative stress in lung epithelial cells. Furthermore, Nupr1 knockout mice exhibit mitochondrial abnormalities, increased oxidative damage, and lung tissue changes consistent with COPD pathology. Collectively, our findings establish NUPR1 as a critical regulator of ferroptosis, stress responses, mitochondrial integrity, and metabolic balance in the lung, highlighting its potential contribution to COPD pathogenesis.
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BibTeX
@article{nouws2026ferroptosis,
title = {{The ferroptosis inhibitor NUPR1 coordinates the mitochondrial response to oxidative stress and cell metabolism during COPD pathogenesis in the lung}},
author = {Jessica Nouws and Saul S. Siller and Tao Yang and So-Jin Kim and Sang-Hun Kim and Patricia Santofimia-Castaño and Juan L. Iovanna and Erica L. Herzog and John E. McDonough and Maor Sauler},
journal = {American journal of physiology. Lung cellular and molecular physiology},
year = {2026},
month = aug,
doi = {10.1152/ajplung.00098.2026},
url = {https://doi.org/10.1152/ajplung.00098.2026},
note = {CC BY},
}
RIS
TY - JOUR
TI - The ferroptosis inhibitor NUPR1 coordinates the mitochondrial response to oxidative stress and cell metabolism during COPD pathogenesis in the lung
AU - Jessica Nouws
AU - Saul S. Siller
AU - Tao Yang
AU - So-Jin Kim
AU - Sang-Hun Kim
AU - Patricia Santofimia-Castaño
AU - Juan L. Iovanna
AU - Erica L. Herzog
AU - John E. McDonough
AU - Maor Sauler
PY - 2026
DA - 2026/08/20
JO - American journal of physiology. Lung cellular and molecular physiology
DO - 10.1152/ajplung.00098.2026
UR - https://doi.org/10.1152/ajplung.00098.2026
AB - Chronic obstructive pulmonary disease (COPD) is characterized by chronic injury and oxidative stress leading to progressive lung tissue destruction. Emerging evidence suggests that regulated cell death pathways, particularly ferroptosis, contribute to COPD pathology. We previously identified the stress response protein and known ferroptosis inhibitor nuclear protein 1 (NUPR1) as markedly downregulated in lung tissue from COPD patients. Here, we demonstrate that NUPR1 inhibition exacerbates iron accumulation, enhances lipid peroxidation, impairs mitochondrial function, disrupts cellular metabolism, and increases oxidative stress in lung epithelial cells. Furthermore, Nupr1 knockout mice exhibit mitochondrial abnormalities, increased oxidative damage, and lung tissue changes consistent with COPD pathology. Collectively, our findings establish NUPR1 as a critical regulator of ferroptosis, stress responses, mitochondrial integrity, and metabolic balance in the lung, highlighting its potential contribution to COPD pathogenesis.
SN - 1040-0605
SN - 1522-1504
ER -