RT Journal Article
T1 Mitochondrial Stress Links Environmental Triggers with Pro-Inflammatory Signaling in Crohn's Disease
A1 Martín-Reyes, Flores
A1 Bernal, Manuel
A1 Rodríguez-Díaz, Cristina
A1 Rodríguez-de los Reyes, Damaris
A1 Ho-Plagaro, Ailec
A1 Rodríguez-Pacheco, Francisca
A1 Camacho- Martel, Laura
A1 Camargo-Camero, Raquel
A1 Rodríguez-González, Francisco J
A1 Alcaín-Martínez, Guillermo
A1 Martin‐Masot, Rafael
A1 Navas-López, Víctor Manuel
A1 Villanueva-Paz, Marina
A1 Lucena, María Isabel
A1 García-Fuentes, Eduardo
A1 López-Gómez, Carlos
K1 Mitocondrias
AB Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have been consistently associated with IBD. We show that NSAIDs induce mitochondrial stress and mitophagy in intestinal epithelial cells. In an altered mitophagy context simulating that observed in IBD patients, NSAID-induced mitochondrial stress leads to the release of mitochondrial components, which act as Danger Associated Molecular Patterns with pro-inflammatory potential. Furthermore, colonic organoids from Crohn's disease patients and healthy donors show activation of the mitochondrial Unfolded Protein Response (UPRmt) upon treatment with ibuprofen. Finally, colon biopsies from Crohn's disease patients in remission or with low-to-moderate activity also show expression of genes involved in UPRmt, while patients with severe activity show no increase compared to healthy donors. Our results suggest the involvement of mitochondria in the mechanisms triggering inflammation in IBD after NSAID use. Moreover, our results highlight the clinical relevance of mitochondrial stress and activation of the UPRmt pathway in the pathophysiology of Crohn's disease.
PB MDPI
YR 2023
FD 2023
LK https://hdl.handle.net/10630/33997
UL https://hdl.handle.net/10630/33997
LA eng
NO Martín-Reyes F, Bernal M, Rodríguez-Díaz C, Rodríguez-de Los Reyes D, Ho-Plagaro A, Rodríguez-Pacheco F, Camacho-Martel L, Camargo-Camero R, Rodríguez-González FJ, Alcain-Martínez G, Martín-Masot R, Navas-López VM, Villanueva-Paz M, Lucena MI, García-Fuentes E, López-Gómez C. Mitochondrial Stress Links Environmental Triggers with Pro-Inflammatory Signaling in Crohn's Disease. Antioxidants (Basel). 2023 Dec 13;12(12):2105.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026