Compartmentalized mitochondrial ferroptosis converges with optineurin-mediated mitophagy to impact airway epithelial cell phenotypes and asthma outcomes.

Autor: Yamada K; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.; Department of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan University, Osaka, 545-8585, Japan., St Croix C; Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Stolz DB; Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Tyurina YY; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Tyurin VA; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Bradley LR; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Kapralov AA; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Deng Y; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.; Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China., Zhou X; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Wei Q; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Liao B; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.; Department of Otolaryngology-Head & Neck Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China., Fukuda N; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.; Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan., Sullivan M; Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Trudeau J; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Ray A; Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, 15260, USA., Kagan VE; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA., Zhao J; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA. JinmingZhao@pitt.edu., Wenzel SE; Department of Environmental and Occupational Health, School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA. swenzel@pitt.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 10; Vol. 15 (1), pp. 5818. Date of Electronic Publication: 2024 Jul 10.
DOI: 10.1038/s41467-024-50222-2
Abstrakt: A stable mitochondrial pool is crucial for healthy cell function and survival. Altered redox biology can adversely affect mitochondria through induction of a variety of cell death and survival pathways, yet the understanding of mitochondria and their dysfunction in primary human cells and in specific disease states, including asthma, is modest. Ferroptosis is traditionally considered an iron dependent, hydroperoxy-phospholipid executed process, which induces cytosolic and mitochondrial damage to drive programmed cell death. However, in this report we identify a lipoxygenase orchestrated, compartmentally-targeted ferroptosis-associated peroxidation process which occurs in a subpopulation of dysfunctional mitochondria, without promoting cell death. Rather, this mitochondrial peroxidation process tightly couples with PTEN-induced kinase (PINK)-1(PINK1)-Parkin-Optineurin mediated mitophagy in an effort to preserve the pool of functional mitochondria and prevent cell death. These combined peroxidation processes lead to altered epithelial cell phenotypes and loss of ciliated cells which associate with worsened asthma severity. Ferroptosis-targeted interventions of this process could preserve healthy mitochondria, reverse cell phenotypic changes and improve disease outcomes.
(© 2024. The Author(s).)
Databáze: MEDLINE
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