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Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease
Here we report the application of a mass spectrometry-based technology, imaging mass cytometry, to perform in-depth proteomic profiling of mitochondrial complexes in single neurons, using metal-conjugated antibodies to label post-mortem human midbrain sections. Mitochondrial dysfunction, particularl...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115071/ https://www.ncbi.nlm.nih.gov/pubmed/33980828 http://dx.doi.org/10.1038/s41531-021-00182-x |
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author | Chen, Chun McDonald, David Blain, Alasdair Sachdeva, Ashwin Bone, Laura Smith, Anna L. M. Warren, Charlotte Pickett, Sarah J. Hudson, Gavin Filby, Andrew Vincent, Amy E. Turnbull, Doug M. Reeve, Amy K. |
author_facet | Chen, Chun McDonald, David Blain, Alasdair Sachdeva, Ashwin Bone, Laura Smith, Anna L. M. Warren, Charlotte Pickett, Sarah J. Hudson, Gavin Filby, Andrew Vincent, Amy E. Turnbull, Doug M. Reeve, Amy K. |
author_sort | Chen, Chun |
collection | PubMed |
description | Here we report the application of a mass spectrometry-based technology, imaging mass cytometry, to perform in-depth proteomic profiling of mitochondrial complexes in single neurons, using metal-conjugated antibodies to label post-mortem human midbrain sections. Mitochondrial dysfunction, particularly deficiency in complex I has previously been associated with the degeneration of dopaminergic neurons in Parkinson’s disease. To further our understanding of the nature of this dysfunction, and to identify Parkinson’s disease specific changes, we validated a panel of antibodies targeting subunits of all five mitochondrial oxidative phosphorylation complexes in dopaminergic neurons from Parkinson’s disease, mitochondrial disease, and control cases. Detailed analysis of the expression profile of these proteins, highlighted heterogeneity between individuals. There is a widespread decrease in expression of all complexes in Parkinson’s neurons, although more severe in mitochondrial disease neurons, however, the combination of affected complexes varies between the two groups. We also provide evidence of a potential neuronal response to mitochondrial dysfunction through a compensatory increase in mitochondrial mass. This study highlights the use of imaging mass cytometry in the assessment and analysis of expression of oxidative phosphorylation proteins, revealing the complexity of deficiencies of these proteins within individual neurons which may contribute to and drive neurodegeneration in Parkinson’s disease. |
format | Online Article Text |
id | pubmed-8115071 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81150712021-05-12 Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease Chen, Chun McDonald, David Blain, Alasdair Sachdeva, Ashwin Bone, Laura Smith, Anna L. M. Warren, Charlotte Pickett, Sarah J. Hudson, Gavin Filby, Andrew Vincent, Amy E. Turnbull, Doug M. Reeve, Amy K. NPJ Parkinsons Dis Article Here we report the application of a mass spectrometry-based technology, imaging mass cytometry, to perform in-depth proteomic profiling of mitochondrial complexes in single neurons, using metal-conjugated antibodies to label post-mortem human midbrain sections. Mitochondrial dysfunction, particularly deficiency in complex I has previously been associated with the degeneration of dopaminergic neurons in Parkinson’s disease. To further our understanding of the nature of this dysfunction, and to identify Parkinson’s disease specific changes, we validated a panel of antibodies targeting subunits of all five mitochondrial oxidative phosphorylation complexes in dopaminergic neurons from Parkinson’s disease, mitochondrial disease, and control cases. Detailed analysis of the expression profile of these proteins, highlighted heterogeneity between individuals. There is a widespread decrease in expression of all complexes in Parkinson’s neurons, although more severe in mitochondrial disease neurons, however, the combination of affected complexes varies between the two groups. We also provide evidence of a potential neuronal response to mitochondrial dysfunction through a compensatory increase in mitochondrial mass. This study highlights the use of imaging mass cytometry in the assessment and analysis of expression of oxidative phosphorylation proteins, revealing the complexity of deficiencies of these proteins within individual neurons which may contribute to and drive neurodegeneration in Parkinson’s disease. Nature Publishing Group UK 2021-05-12 /pmc/articles/PMC8115071/ /pubmed/33980828 http://dx.doi.org/10.1038/s41531-021-00182-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Chen, Chun McDonald, David Blain, Alasdair Sachdeva, Ashwin Bone, Laura Smith, Anna L. M. Warren, Charlotte Pickett, Sarah J. Hudson, Gavin Filby, Andrew Vincent, Amy E. Turnbull, Doug M. Reeve, Amy K. Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease |
title | Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease |
title_full | Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease |
title_fullStr | Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease |
title_full_unstemmed | Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease |
title_short | Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease |
title_sort | imaging mass cytometry reveals generalised deficiency in oxphos complexes in parkinson’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115071/ https://www.ncbi.nlm.nih.gov/pubmed/33980828 http://dx.doi.org/10.1038/s41531-021-00182-x |
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