Journal article
Mitochondrial uncoupling proteins protect human airway epithelial ciliated cells from oxidative damage
Proceedings of the National Academy of Sciences - PNAS, Vol.121(10), e2318771121
03/05/2024
DOI: 10.1073/pnas.2318771121
PMCID: PMC10927548
PMID: 38416686
Abstract
Apical cilia on epithelial cells defend the lung by propelling pathogens and particulates out of the respiratory airways. Ciliated cells produce ATP that powers cilia beating by densely grouping mitochondria just beneath the apical membrane. However, this efficient localization comes at a cost because electrons leaked during oxidative phosphorylation react with molecular oxygen to form superoxide, and thus, the cluster of mitochondria creates a hotspot for oxidant production. The relatively high oxygen concentration overlying airway epithelia further intensifies the risk of generating superoxide. Thus, airway ciliated cells face a unique challenge of producing harmful levels of oxidants. However, surprisingly, highly ciliated epithelia produce less reactive oxygen species (ROS) than epithelia with few ciliated cells. Compared to other airway cell types, ciliated cells express high levels of mitochondrial uncoupling proteins, UCP2 and UCP5. These proteins decrease mitochondrial protonmotive force and thereby reduce production of ROS. As a result, lipid peroxidation, a marker of oxidant injury, decreases. However, mitochondrial uncoupling proteins exact a price for decreasing oxidant production; they decrease the fraction of mitochondrial respiration that generates ATP. These findings indicate that ciliated cells sacrifice mitochondrial efficiency in exchange for safety from damaging oxidation. Employing uncoupling proteins to prevent oxidant production, instead of relying solely on antioxidants to decrease postproduction oxidant levels, may offer an advantage for targeting a local area of intense ROS generation.
Details
- Title: Subtitle
- Mitochondrial uncoupling proteins protect human airway epithelial ciliated cells from oxidative damage
- Creators
- Akansha Jain - University of IowaBo Ram Kim - HHMI, Department of Internal Medicine, University of Iowa, Iowa City, IA 52242Wenjie Yu - University of IowaThomas O Moninger - University of IowaPhilip H Karp - University of IowaBrett A Wagner - University of IowaMichael J Welsh - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.121(10), e2318771121
- DOI
- 10.1073/pnas.2318771121
- PMID
- 38416686
- PMCID
- PMC10927548
- NLM abbreviation
- Proc Natl Acad Sci U S A
- eISSN
- 1091-6490
- Grant note
- HL152960 / HHS | National Institutes of Health (NIH) HL09184 / HHS | National Institutes of Health (NIH) N/A / Howard Hughes Medical Institute (HHMI) N/A / Roy J. Carver Charitable Trust (RJCCT)
- Language
- English
- Date published
- 03/05/2024
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984563452302771
Metrics
7 Record Views