Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease

Abstract 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, pa...

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Autores principales:	Chun Chen, David McDonald, Alasdair Blain, Ashwin Sachdeva, Laura Bone, Anna L. M. Smith, Charlotte Warren, Sarah J. Pickett, Gavin Hudson, Andrew Filby, Amy E. Vincent, Doug M. Turnbull, Amy K. Reeve
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/d11c8df42c1742fbb028839471ea2b10
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spelling	oai:doaj.org-article:d11c8df42c1742fbb028839471ea2b102021-12-02T15:54:55ZImaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease10.1038/s41531-021-00182-x2373-8057https://doaj.org/article/d11c8df42c1742fbb028839471ea2b102021-05-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00182-xhttps://doaj.org/toc/2373-8057Abstract 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.Chun ChenDavid McDonaldAlasdair BlainAshwin SachdevaLaura BoneAnna L. M. SmithCharlotte WarrenSarah J. PickettGavin HudsonAndrew FilbyAmy E. VincentDoug M. TurnbullAmy K. ReeveNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurology. Diseases of the nervous system RC346-429 Chun Chen David McDonald Alasdair Blain Ashwin Sachdeva Laura Bone Anna L. M. Smith Charlotte Warren Sarah J. Pickett Gavin Hudson Andrew Filby Amy E. Vincent Doug M. Turnbull Amy K. Reeve Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease
description	Abstract 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	article
author	Chun Chen David McDonald Alasdair Blain Ashwin Sachdeva Laura Bone Anna L. M. Smith Charlotte Warren Sarah J. Pickett Gavin Hudson Andrew Filby Amy E. Vincent Doug M. Turnbull Amy K. Reeve
author_facet	Chun Chen David McDonald Alasdair Blain Ashwin Sachdeva Laura Bone Anna L. M. Smith Charlotte Warren Sarah J. Pickett Gavin Hudson Andrew Filby Amy E. Vincent Doug M. Turnbull Amy K. Reeve
author_sort	Chun Chen
title	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_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_sort	imaging mass cytometry reveals generalised deficiency in oxphos complexes in parkinson’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d11c8df42c1742fbb028839471ea2b10
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Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease

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