Enhanced Mitophagy in Cholesteatoma Epithelial Cells.


Journal

Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
ISSN: 1537-4505
Titre abrégé: Otol Neurotol
Pays: United States
ID NLM: 100961504

Informations de publication

Date de publication:
01 10 2023
Historique:
medline: 15 9 2023
pubmed: 17 8 2023
entrez: 17 8 2023
Statut: ppublish

Résumé

Mitophagy may have a potential role in the pathogenesis of acquired cholesteatoma. Enhanced mitophagy has been proven to be involved in various cancers. However, its role in the pathogenesis of cholesteatoma, which shares some common features with cancer, is controversial. This study investigated mitophagy in cholesteatoma epithelial cells. The autophagy protein markers LC3-II and p62 and mitophagy proteins BNIP3, Parkin, and PINK1 were analyzed in cholesteatoma epithelial cells and external auditory canal epithelium cells by immunoblotting. The results were confirmed by immunohistochemistry. Adenovirus Ad-mCherry-GFP-LC3B and Ad-GFP-LC3B were used to evaluate autophagic activity. Transmission electron microscopy was used to observe and analyze autophagosomes. LC3-II expression was increased in cholesteatoma cells, whereas soluble and insoluble p62 levels were decreased. The expressions of BNIP3, Parkin, and PINK1 were higher in total protein and mitochondrial protein of cholesteatoma cells compared with normal external auditory canal epithelium cells. Autophagic activity was increased in cholesteatoma cells compared with normal external auditory canal epithelium cells. Mitophagy was enhanced in cholesteatoma epithelial cells and may have a potential role in the pathogenesis of acquired cholesteatoma.

Sections du résumé

HYPOTHESIS
Mitophagy may have a potential role in the pathogenesis of acquired cholesteatoma.
BACKGROUND
Enhanced mitophagy has been proven to be involved in various cancers. However, its role in the pathogenesis of cholesteatoma, which shares some common features with cancer, is controversial. This study investigated mitophagy in cholesteatoma epithelial cells.
METHODS
The autophagy protein markers LC3-II and p62 and mitophagy proteins BNIP3, Parkin, and PINK1 were analyzed in cholesteatoma epithelial cells and external auditory canal epithelium cells by immunoblotting. The results were confirmed by immunohistochemistry. Adenovirus Ad-mCherry-GFP-LC3B and Ad-GFP-LC3B were used to evaluate autophagic activity. Transmission electron microscopy was used to observe and analyze autophagosomes.
RESULTS
LC3-II expression was increased in cholesteatoma cells, whereas soluble and insoluble p62 levels were decreased. The expressions of BNIP3, Parkin, and PINK1 were higher in total protein and mitochondrial protein of cholesteatoma cells compared with normal external auditory canal epithelium cells. Autophagic activity was increased in cholesteatoma cells compared with normal external auditory canal epithelium cells.
CONCLUSION
Mitophagy was enhanced in cholesteatoma epithelial cells and may have a potential role in the pathogenesis of acquired cholesteatoma.

Identifiants

pubmed: 37590884
doi: 10.1097/MAO.0000000000003986
pii: 00129492-990000000-00379
doi:

Substances chimiques

Ubiquitin-Protein Ligases EC 2.3.2.27
Protein Kinases EC 2.7.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e688-e694

Informations de copyright

Copyright © 2023, Otology & Neurotology, Inc.

Déclaration de conflit d'intérêts

The authors disclose no conflicts of interest.

Références

Paparella MM, Schachern PA, Cureoglu S. Chronic silent otitis media. ORL J Otorhinolaryngol Relat Spec 2022;64:65–72.
Robinson JM. Cholesteatoma: Skin in the wrong place. J R Soc Med 1997;90:93–6.
Gray JD. The chronic ear. The treatment of cholesteatoma in children. Proc R Soc Med 1964;57:769–71.
Kuo CL, Shiao AS, Yung M, et al. Updates and knowledge gaps in cholesteatoma research. Biomed Res Int 2015;2015:854024.
Prescott CA. Cholesteatoma in children—The experience at the red cross war memorial Children's Hospital in South Africa 1988–1996. Int J Pediatr Otorhinolaryngol 1999;49:15–9.
Diom ES, Cisse Z, Tall A, et al. Management of acquired cholesteatoma in children: A 15 year review in ENT service of CHNU de FANN Dakar. Int J Pediatr Otorhinolaryngol 2013;77:1998–2003.
Kuo CL. Etiopathogenesis of acquired cholesteatoma: Prominent theories and recent advances in biomolecular research. Laryngoscope 2015;125:234–40.
Yung M, Tono T, Olszewska E, et al. EAONO/JOS joint consensus statements on the definitions, classification and staging of middle ear cholesteatoma. J Int Adv Otol 2017;13:1–8.
Kuo CL, Shiao AS, Liao WH, Ho CY, Lien CF. Can long-term hearing preservation be expected in children following cholesteatoma surgery? Results from a 14-year-long study of atticotomy-limited mastoidectomy with cartilage reconstruction. Audiol Neurootol 2012;17:386–94.
Nikolopoulos TP, Gerbesiotis P. Surgical management of cholesteatoma: the two main options and the third way—Atticotomy/limited mastoidectomy. Int J Pediatr Otorhinolaryngol 2009;73:1222–7.
Lu Y, Li Z, Zhang S, et al. Cellular mitophagy: mechanism, roles in diseases and small molecule pharmacological regulation. Theranostics 2023;13:736–66.
Montava-Garriga L, Ganley IG. Outstanding questions in mitophagy: What we do and do not know. J Mol Biol 2020;432:206–30.
Onishi M, Yamano K, Sato M, Matsuda N, Okamoto K. Molecular mechanisms and physiological functions of mitophagy. EMBO J 2021;40:e104705.
Levy JMM, Towers CG, Thorburn A. Targeting autophagy in cancer. Nat Rev Cancer 2017;17:528–42.
Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol 2010;22:124–31.
Shih CP, Lee JT, Chen HK, et al. Comparison of changes in mitochondrial bioenergetics between keratinocytes in human external auditory canal skin and cholesteatomas from normoxia to hypoxia. Sci Rep 2018;8:125.
Li Q, Ao Y, Yu Q, Zhou S. Role of autophagy in acquired cholesteatoma. Otol Neurotol 2019;40:e993–8.
Jung J, Jung SY, Kim MG, et al. Comparison of autophagy mRNA expression between chronic otitis media with and without cholesteatoma. J Audiol Otol 2020;24:191–7.
Ho KY, Huang CJ, Hung CC, et al. Autophagy is deficient and may be negatively regulated by SERPINB3 in middle ear cholesteatoma. OtolNeurotol 2020;41:e881–8.
Carlsson SR, Simonsen A. Membrane dynamics in autophagosome biogenesis. J Cell Sci 2015;128:193–205.
Murugan S, Amaravadi RK. Methods for studying autophagy within the tumor microenvironment. Adv Exp Med Biol 2016;899:145–66.
Yamada T, Dawson TM, Yanagawa T, Iijima M, Sesaki H. SQSTM1/p62 promotes mitochondrial ubiquitination independently of PINK1 and PRKN/parkin in mitophagy. Autophagy 2019;15:2012–8.
Lin Q, Li S, Jiang N, et al. Inhibiting NLRP3 inflammasome attenuates apoptosis in contrast-induced acute kidney injury through the upregulation of HIF1A and BNIP3-mediated mitophagy. Autophagy 2021;17:2975–90.
Geisler S, Holmström KM, Skujat D, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 2010;12:119–31.
Fang EF, Palikaras K, Sun N, et al. In vitro and in vivo detection of mitophagy in human cells, C. elegans , and mice. J Vis Exp 2017;129:56301.
Hsu P, Shi Y. Regulation of autophagy by mitochondrial phospholipids in health and diseases. Biochim Biophys Acta Mol Cell Biol Lipids 2017;1862:114–29.
Bento CF, Renna M, Ghislat G, et al. Mammalian autophagy: How does it work? Annu Rev Biochem 2016;85:685–713.

Auteurs

Quan-Cheng Li (QC)

Department of Otolaryngology-Head and Neck Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH