PHB2 Alleviates Neurotoxicity of Prion Peptide PrP<sup>106–126</sup> via PINK1/Parkin-Dependent Mitophagy
2023
Xiaohui Zheng | Kun Liu | Qingqing Xie | Hangkuo Xin | Wei Chen | Shengyu Lin | Danqi Feng | Ting Zhu
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<sup>106–126</sup> as a cell model for prion diseases. We examined the role of PHB2 in PrP<sup>106–126</sup>-induced mitophagy using Western blotting and immunofluorescence microscopy and assessed the function of PHB2 in PrP<sup>106–126</sup>-induced neuronal death using the cell viability assay and the TUNEL assay. The results showed that PrP<sup>106–126</sup> induced mitochondrial morphological abnormalities and mitophagy in primary cortical neurons. PHB2 was found to be indispensable for PrP<sup>106–126</sup>-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<sup>106–126</sup>, whereas the overexpression of PHB2 alleviated PrP<sup>106–126</sup> neuronal toxicity. Taken together, this study demonstrated that PHB2 is indispensable for PINK1/Parkin-mediated mitophagy in PrP<sup>106–126</sup>-treated neurons and protects neurons against the neurotoxicity of the prion peptide.
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