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PHB2 Alleviates Neurotoxicity of Prion Peptide PrP(106–126) via PINK1/Parkin-Dependent Mitophagy

Prion diseases are a group of neurodegenerative diseases characterized by mitochondrial dysfunction and neuronal death. Mitophagy is a selective form of macroautophagy that clears injured mitochondria. Prohibitin 2 (PHB2) has been identified as a novel inner membrane mitophagy receptor that mediates...

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Detalles Bibliográficos
Autores principales: Zheng, Xiaohui, Liu, Kun, Xie, Qingqing, Xin, Hangkuo, Chen, Wei, Lin, Shengyu, Feng, Danqi, Zhu, Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647768/
https://www.ncbi.nlm.nih.gov/pubmed/37958902
http://dx.doi.org/10.3390/ijms242115919
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author Zheng, Xiaohui
Liu, Kun
Xie, Qingqing
Xin, Hangkuo
Chen, Wei
Lin, Shengyu
Feng, Danqi
Zhu, Ting
author_facet Zheng, Xiaohui
Liu, Kun
Xie, Qingqing
Xin, Hangkuo
Chen, Wei
Lin, Shengyu
Feng, Danqi
Zhu, Ting
author_sort Zheng, Xiaohui
collection PubMed
description Prion diseases are a group of neurodegenerative diseases characterized by mitochondrial dysfunction and neuronal death. Mitophagy is a selective form of macroautophagy that clears injured mitochondria. Prohibitin 2 (PHB2) has been identified as a novel inner membrane mitophagy receptor that mediates mitophagy. However, the role of PHB2 in prion diseases remains unclear. In this study, we isolated primary cortical neurons from rats and used the neurotoxic prion peptide PrP(106–126) as a cell model for prion diseases. We examined the role of PHB2 in PrP(106–126)-induced mitophagy using Western blotting and immunofluorescence microscopy and assessed the function of PHB2 in PrP(106–126)-induced neuronal death using the cell viability assay and the TUNEL assay. The results showed that PrP(106–126) induced mitochondrial morphological abnormalities and mitophagy in primary cortical neurons. PHB2 was found to be indispensable for PrP(106–126)-induced mitophagy and was involved in the accumulation of PINK1 and recruitment of Parkin to mitochondria in primary neurons. Additionally, PHB2 depletion exacerbated neuronal cell death induced by PrP(106–126), whereas the overexpression of PHB2 alleviated PrP(106–126) neuronal toxicity. Taken together, this study demonstrated that PHB2 is indispensable for PINK1/Parkin-mediated mitophagy in PrP(106–126)-treated neurons and protects neurons against the neurotoxicity of the prion peptide.
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spelling pubmed-106477682023-11-02 PHB2 Alleviates Neurotoxicity of Prion Peptide PrP(106–126) via PINK1/Parkin-Dependent Mitophagy Zheng, Xiaohui Liu, Kun Xie, Qingqing Xin, Hangkuo Chen, Wei Lin, Shengyu Feng, Danqi Zhu, Ting Int J Mol Sci Article Prion diseases are a group of neurodegenerative diseases characterized by mitochondrial dysfunction and neuronal death. Mitophagy is a selective form of macroautophagy that clears injured mitochondria. Prohibitin 2 (PHB2) has been identified as a novel inner membrane mitophagy receptor that mediates mitophagy. However, the role of PHB2 in prion diseases remains unclear. In this study, we isolated primary cortical neurons from rats and used the neurotoxic prion peptide PrP(106–126) as a cell model for prion diseases. We examined the role of PHB2 in PrP(106–126)-induced mitophagy using Western blotting and immunofluorescence microscopy and assessed the function of PHB2 in PrP(106–126)-induced neuronal death using the cell viability assay and the TUNEL assay. The results showed that PrP(106–126) induced mitochondrial morphological abnormalities and mitophagy in primary cortical neurons. PHB2 was found to be indispensable for PrP(106–126)-induced mitophagy and was involved in the accumulation of PINK1 and recruitment of Parkin to mitochondria in primary neurons. Additionally, PHB2 depletion exacerbated neuronal cell death induced by PrP(106–126), whereas the overexpression of PHB2 alleviated PrP(106–126) neuronal toxicity. Taken together, this study demonstrated that PHB2 is indispensable for PINK1/Parkin-mediated mitophagy in PrP(106–126)-treated neurons and protects neurons against the neurotoxicity of the prion peptide. MDPI 2023-11-02 /pmc/articles/PMC10647768/ /pubmed/37958902 http://dx.doi.org/10.3390/ijms242115919 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zheng, Xiaohui
Liu, Kun
Xie, Qingqing
Xin, Hangkuo
Chen, Wei
Lin, Shengyu
Feng, Danqi
Zhu, Ting
PHB2 Alleviates Neurotoxicity of Prion Peptide PrP(106–126) via PINK1/Parkin-Dependent Mitophagy
title PHB2 Alleviates Neurotoxicity of Prion Peptide PrP(106–126) via PINK1/Parkin-Dependent Mitophagy
title_full PHB2 Alleviates Neurotoxicity of Prion Peptide PrP(106–126) via PINK1/Parkin-Dependent Mitophagy
title_fullStr PHB2 Alleviates Neurotoxicity of Prion Peptide PrP(106–126) via PINK1/Parkin-Dependent Mitophagy
title_full_unstemmed PHB2 Alleviates Neurotoxicity of Prion Peptide PrP(106–126) via PINK1/Parkin-Dependent Mitophagy
title_short PHB2 Alleviates Neurotoxicity of Prion Peptide PrP(106–126) via PINK1/Parkin-Dependent Mitophagy
title_sort phb2 alleviates neurotoxicity of prion peptide prp(106–126) via pink1/parkin-dependent mitophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10647768/
https://www.ncbi.nlm.nih.gov/pubmed/37958902
http://dx.doi.org/10.3390/ijms242115919
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