Cargando…
Prohibitin 2 is Involved in Parkin-Mediated Mitophagy in Urothelial Cells of Cattle Infected with Bovine Papillomavirus
Prohibitin 2 (PHB2), an inner mitochondrial membrane (IMM) protein, has recently been identified as a novel receptor involved in parkin-mediated mitophagy. In the field of veterinary medicine, the role of PHB2 in parkin-mediated mitophagy was described, for the first time, in urothelial cells of cat...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460215/ https://www.ncbi.nlm.nih.gov/pubmed/32751272 http://dx.doi.org/10.3390/pathogens9080621 |
_version_ | 1783576550575177728 |
---|---|
author | De Falco, Francesca Gentile, Ivan Cerino, Pellegrino Cutarelli, Anna Catoi, Cornel Roperto, Sante |
author_facet | De Falco, Francesca Gentile, Ivan Cerino, Pellegrino Cutarelli, Anna Catoi, Cornel Roperto, Sante |
author_sort | De Falco, Francesca |
collection | PubMed |
description | Prohibitin 2 (PHB2), an inner mitochondrial membrane (IMM) protein, has recently been identified as a novel receptor involved in parkin-mediated mitophagy. In the field of veterinary medicine, the role of PHB2 in parkin-mediated mitophagy was described, for the first time, in urothelial cells of cattle, naturally infected with bovine papillomavirus (BPV). The BPV2 and BPV13 E5 oncoprotein, responsible for abortive infections in urothelial cells, was detected by RT-PCR. Severe ultrastructural abnormalities of the inner mitochondrial membrane were detected using transmission electron microscopy. PHB2 formed a functional complex with PHB1. PHB2 was significantly overexpressed in mitochondrial fractions from urothelial mucosa samples taken from cattle harbouring BPV infection. PHB2 overexpression could be attributed to mitochondrial dysfunction, as its expression levels in the cytosolic, microsomal, and nuclear fractions were seen to be unmodified. Immunoprecipitation studies revealed the interaction between PHB2 and phosphorylated forms of both PINK1 and parkin. Furthermore, PHB2 interacted with LC3-II, a marker of autophagosomal membranes and autophagy receptors, such as p62 and optineurin. PHB2 was shown to interact with transcription factor EB (TFEB), which is activated following parkin-mediated mitophagy, and embryonic stem cell-expressed Ras (ERAS), a constitutive protein coded by ERas. Western blot analysis revealed a significant overexpression of unphosphorylated TFEB in mitochondrial and nuclear fractions from urothelial mucosa samples from cattle suffering from BPV infection. Finally, PHB2 interacted with ERAS, believed to be involved in mitophagosome maturation. Taken together, the molecular and ultrastructural findings of this study suggested that BPV infection is responsible for parkin-dependent mitophagy, in the pathway of which PHB2 plays a crucial role. |
format | Online Article Text |
id | pubmed-7460215 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74602152020-09-02 Prohibitin 2 is Involved in Parkin-Mediated Mitophagy in Urothelial Cells of Cattle Infected with Bovine Papillomavirus De Falco, Francesca Gentile, Ivan Cerino, Pellegrino Cutarelli, Anna Catoi, Cornel Roperto, Sante Pathogens Article Prohibitin 2 (PHB2), an inner mitochondrial membrane (IMM) protein, has recently been identified as a novel receptor involved in parkin-mediated mitophagy. In the field of veterinary medicine, the role of PHB2 in parkin-mediated mitophagy was described, for the first time, in urothelial cells of cattle, naturally infected with bovine papillomavirus (BPV). The BPV2 and BPV13 E5 oncoprotein, responsible for abortive infections in urothelial cells, was detected by RT-PCR. Severe ultrastructural abnormalities of the inner mitochondrial membrane were detected using transmission electron microscopy. PHB2 formed a functional complex with PHB1. PHB2 was significantly overexpressed in mitochondrial fractions from urothelial mucosa samples taken from cattle harbouring BPV infection. PHB2 overexpression could be attributed to mitochondrial dysfunction, as its expression levels in the cytosolic, microsomal, and nuclear fractions were seen to be unmodified. Immunoprecipitation studies revealed the interaction between PHB2 and phosphorylated forms of both PINK1 and parkin. Furthermore, PHB2 interacted with LC3-II, a marker of autophagosomal membranes and autophagy receptors, such as p62 and optineurin. PHB2 was shown to interact with transcription factor EB (TFEB), which is activated following parkin-mediated mitophagy, and embryonic stem cell-expressed Ras (ERAS), a constitutive protein coded by ERas. Western blot analysis revealed a significant overexpression of unphosphorylated TFEB in mitochondrial and nuclear fractions from urothelial mucosa samples from cattle suffering from BPV infection. Finally, PHB2 interacted with ERAS, believed to be involved in mitophagosome maturation. Taken together, the molecular and ultrastructural findings of this study suggested that BPV infection is responsible for parkin-dependent mitophagy, in the pathway of which PHB2 plays a crucial role. MDPI 2020-07-29 /pmc/articles/PMC7460215/ /pubmed/32751272 http://dx.doi.org/10.3390/pathogens9080621 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article De Falco, Francesca Gentile, Ivan Cerino, Pellegrino Cutarelli, Anna Catoi, Cornel Roperto, Sante Prohibitin 2 is Involved in Parkin-Mediated Mitophagy in Urothelial Cells of Cattle Infected with Bovine Papillomavirus |
title | Prohibitin 2 is Involved in Parkin-Mediated Mitophagy in Urothelial Cells of Cattle Infected with Bovine Papillomavirus |
title_full | Prohibitin 2 is Involved in Parkin-Mediated Mitophagy in Urothelial Cells of Cattle Infected with Bovine Papillomavirus |
title_fullStr | Prohibitin 2 is Involved in Parkin-Mediated Mitophagy in Urothelial Cells of Cattle Infected with Bovine Papillomavirus |
title_full_unstemmed | Prohibitin 2 is Involved in Parkin-Mediated Mitophagy in Urothelial Cells of Cattle Infected with Bovine Papillomavirus |
title_short | Prohibitin 2 is Involved in Parkin-Mediated Mitophagy in Urothelial Cells of Cattle Infected with Bovine Papillomavirus |
title_sort | prohibitin 2 is involved in parkin-mediated mitophagy in urothelial cells of cattle infected with bovine papillomavirus |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460215/ https://www.ncbi.nlm.nih.gov/pubmed/32751272 http://dx.doi.org/10.3390/pathogens9080621 |
work_keys_str_mv | AT defalcofrancesca prohibitin2isinvolvedinparkinmediatedmitophagyinurothelialcellsofcattleinfectedwithbovinepapillomavirus AT gentileivan prohibitin2isinvolvedinparkinmediatedmitophagyinurothelialcellsofcattleinfectedwithbovinepapillomavirus AT cerinopellegrino prohibitin2isinvolvedinparkinmediatedmitophagyinurothelialcellsofcattleinfectedwithbovinepapillomavirus AT cutarellianna prohibitin2isinvolvedinparkinmediatedmitophagyinurothelialcellsofcattleinfectedwithbovinepapillomavirus AT catoicornel prohibitin2isinvolvedinparkinmediatedmitophagyinurothelialcellsofcattleinfectedwithbovinepapillomavirus AT ropertosante prohibitin2isinvolvedinparkinmediatedmitophagyinurothelialcellsofcattleinfectedwithbovinepapillomavirus |