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α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line

α-synuclein (αSyn) is a small neuronal protein whose accumulation correlates with Parkinson’s disease. αSyn A53T mutant impairs mitochondrial functions by affecting substrate import within the organelle, activity of complex I and the maximal respiratory capacity. However, the precise mechanism initi...

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Detalles Bibliográficos
Autores principales: Risiglione, Pierpaolo, Cubisino, Salvatore Antonio Maria, Lipari, Cristiana Lucia Rita, De Pinto, Vito, Messina, Angela, Magrì, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225574/
https://www.ncbi.nlm.nih.gov/pubmed/35743925
http://dx.doi.org/10.3390/life12060894
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author Risiglione, Pierpaolo
Cubisino, Salvatore Antonio Maria
Lipari, Cristiana Lucia Rita
De Pinto, Vito
Messina, Angela
Magrì, Andrea
author_facet Risiglione, Pierpaolo
Cubisino, Salvatore Antonio Maria
Lipari, Cristiana Lucia Rita
De Pinto, Vito
Messina, Angela
Magrì, Andrea
author_sort Risiglione, Pierpaolo
collection PubMed
description α-synuclein (αSyn) is a small neuronal protein whose accumulation correlates with Parkinson’s disease. αSyn A53T mutant impairs mitochondrial functions by affecting substrate import within the organelle, activity of complex I and the maximal respiratory capacity. However, the precise mechanism initiating the bioenergetic dysfunction is not clearly understood yet. By overexpressing αSyn A53T in SH-SY5Y cells, we investigated the specific changes in the mitochondrial respiratory profile using High-Resolution Respirometry. We found that αSyn A53T increases dissipative fluxes across the intermembrane mitochondrial space: this does not compromise the oxygen flows devoted to ATP production while it reduces the bioenergetic excess capacity of mitochondria, providing a possible explanation of the increased cell susceptibility observed in the presence of further stress stimuli.
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spelling pubmed-92255742022-06-24 α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line Risiglione, Pierpaolo Cubisino, Salvatore Antonio Maria Lipari, Cristiana Lucia Rita De Pinto, Vito Messina, Angela Magrì, Andrea Life (Basel) Article α-synuclein (αSyn) is a small neuronal protein whose accumulation correlates with Parkinson’s disease. αSyn A53T mutant impairs mitochondrial functions by affecting substrate import within the organelle, activity of complex I and the maximal respiratory capacity. However, the precise mechanism initiating the bioenergetic dysfunction is not clearly understood yet. By overexpressing αSyn A53T in SH-SY5Y cells, we investigated the specific changes in the mitochondrial respiratory profile using High-Resolution Respirometry. We found that αSyn A53T increases dissipative fluxes across the intermembrane mitochondrial space: this does not compromise the oxygen flows devoted to ATP production while it reduces the bioenergetic excess capacity of mitochondria, providing a possible explanation of the increased cell susceptibility observed in the presence of further stress stimuli. MDPI 2022-06-15 /pmc/articles/PMC9225574/ /pubmed/35743925 http://dx.doi.org/10.3390/life12060894 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Risiglione, Pierpaolo
Cubisino, Salvatore Antonio Maria
Lipari, Cristiana Lucia Rita
De Pinto, Vito
Messina, Angela
Magrì, Andrea
α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line
title α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line
title_full α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line
title_fullStr α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line
title_full_unstemmed α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line
title_short α-Synuclein A53T Promotes Mitochondrial Proton Gradient Dissipation and Depletion of the Organelle Respiratory Reserve in a Neuroblastoma Cell Line
title_sort α-synuclein a53t promotes mitochondrial proton gradient dissipation and depletion of the organelle respiratory reserve in a neuroblastoma cell line
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225574/
https://www.ncbi.nlm.nih.gov/pubmed/35743925
http://dx.doi.org/10.3390/life12060894
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