PHB2 Alleviates Neurotoxicity of Prion Peptide PrP ^106-126 via PINK1/Parkin-Dependent Mitophagy.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Neurotoxicity Syndromes* ; Prion Diseases* ; Prions*; Animals ; Rats ; Mitophagy/physiology ; Peptides/pharmacology ; Protein Kinases/metabolism ; Ubiquitin-Protein Ligases/metabolism

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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No. 32002250 National Natural Science Foundation of China

Keywords: PHB2; PINK1/Parkin; PrP106–126; mitophagy; neuronal death; prion disease; prion peptide

0 (Peptides)
0 (Prions)
EC 2.7.- (Protein Kinases)
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
0 (Phb2 protein, rat)

Date Created: 20231114 Date Completed: 20231117 Latest Revision: 20231122

20231215

PMC10647768

10.3390/ijms242115919

37958902