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Autophagy aggravates multi-walled carbon nanotube-induced ferroptosis by suppressing PGC-1 dependent-mitochondrial biogenesis in lung epithelial cells.
- Source :
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Chemico-biological interactions [Chem Biol Interact] 2024 Sep 01; Vol. 400, pp. 111158. Date of Electronic Publication: 2024 Jul 19. - Publication Year :
- 2024
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Abstract
- Multi-walled carbon nanotube (MWCNT) induced respiratory toxicity has become a growing concern, with ferroptosis emerging as a novel mechanism implicated in various respiratory diseases. However, whether ferroptosis is involved in MWCNT-elicited lung injury and the underlying molecular mechanisms warrant further exploration. In this study, we found that MWCNT-induced ferroptosis is autophagy-dependent, contributing to its cellular toxicity. Inhibiting of autophagy by pharmacological inhibitors 3-MA or ATG5 gene knockdown significantly attenuated MWCNT-induced ferroptosis, concomitant with rescued mitochondrial biogenesis. Rapamycin, the autophagy agonist, exacerbated the mitochondrial damage and MWCNT-induced ferroptosis. Moreover, lentivirus-mediated overexpression of PGC-1α inhibited ferroptosis, while inhibition of PGC-1α aggravated ferroptosis. In summary, our study unveils ferroptosis as a novel mechanism underlying MWCNT-induced respiratory toxicity, with autophagy promoting MWCNT-induced ferroptosis by hindering PGC-1α-dependent mitochondrial biogenesis.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Epithelial Cells metabolism
Epithelial Cells drug effects
Mitochondria metabolism
Mitochondria drug effects
Organelle Biogenesis
Autophagy-Related Protein 5 metabolism
Autophagy-Related Protein 5 genetics
Animals
Sirolimus pharmacology
Mice
Cell Line
Nanotubes, Carbon toxicity
Ferroptosis drug effects
Autophagy drug effects
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha genetics
Lung drug effects
Lung metabolism
Lung pathology
Lung cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7786
- Volume :
- 400
- Database :
- MEDLINE
- Journal :
- Chemico-biological interactions
- Publication Type :
- Academic Journal
- Accession number :
- 39033796
- Full Text :
- https://doi.org/10.1016/j.cbi.2024.111158