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Effect of Chronic Stress Present in Fibroblasts Derived from Patients with a Sporadic Form of AD on Mitochondrial Function and Mitochondrial Turnover
Although the sporadic form of Alzheimer’s disease (AD) is the prevalent form, the cellular events underlying the disease pathogenesis have not been fully characterized. Accumulating evidence points to mitochondrial dysfunction as one of the events responsible for AD progression. We investigated mito...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229029/ https://www.ncbi.nlm.nih.gov/pubmed/34200581 http://dx.doi.org/10.3390/antiox10060938 |
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author | Drabik, Karolina Malińska, Dominika Piecyk, Karolina Dębska-Vielhaber, Grażyna Vielhaber, Stefan Duszyński, Jerzy Szczepanowska, Joanna |
author_facet | Drabik, Karolina Malińska, Dominika Piecyk, Karolina Dębska-Vielhaber, Grażyna Vielhaber, Stefan Duszyński, Jerzy Szczepanowska, Joanna |
author_sort | Drabik, Karolina |
collection | PubMed |
description | Although the sporadic form of Alzheimer’s disease (AD) is the prevalent form, the cellular events underlying the disease pathogenesis have not been fully characterized. Accumulating evidence points to mitochondrial dysfunction as one of the events responsible for AD progression. We investigated mitochondrial function in fibroblasts collected from patients diagnosed with the sporadic form of AD (sAD), placing a particular focus on mitochondrial turnover. We measured mitochondrial biogenesis and autophagic clearance, and evaluated the presence of bioenergetic stress in sAD cells. The mitochondrial turnover was clearly lower in the fibroblasts from sAD patients than in the fibroblasts from the control subjects, and the levels of many proteins regulating mitochondrial biogenesis, autophagy and mitophagy were decreased in patient cells. Additionally, the sAD fibroblasts had slightly higher mitochondrial superoxide levels and impaired antioxidant defense. Mitochondrial turnover undergoes feedback regulation through mitochondrial retrograde signaling, which is responsible for the maintenance of optimal mitochondrial functioning, and mitochondria-derived ROS participate as signaling molecules in this process. Our results showed that in sAD patients cells, there is a shift in the balance of mitochondrial function, possibly in response to the presence of cellular stress related to disease development. |
format | Online Article Text |
id | pubmed-8229029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82290292021-06-26 Effect of Chronic Stress Present in Fibroblasts Derived from Patients with a Sporadic Form of AD on Mitochondrial Function and Mitochondrial Turnover Drabik, Karolina Malińska, Dominika Piecyk, Karolina Dębska-Vielhaber, Grażyna Vielhaber, Stefan Duszyński, Jerzy Szczepanowska, Joanna Antioxidants (Basel) Article Although the sporadic form of Alzheimer’s disease (AD) is the prevalent form, the cellular events underlying the disease pathogenesis have not been fully characterized. Accumulating evidence points to mitochondrial dysfunction as one of the events responsible for AD progression. We investigated mitochondrial function in fibroblasts collected from patients diagnosed with the sporadic form of AD (sAD), placing a particular focus on mitochondrial turnover. We measured mitochondrial biogenesis and autophagic clearance, and evaluated the presence of bioenergetic stress in sAD cells. The mitochondrial turnover was clearly lower in the fibroblasts from sAD patients than in the fibroblasts from the control subjects, and the levels of many proteins regulating mitochondrial biogenesis, autophagy and mitophagy were decreased in patient cells. Additionally, the sAD fibroblasts had slightly higher mitochondrial superoxide levels and impaired antioxidant defense. Mitochondrial turnover undergoes feedback regulation through mitochondrial retrograde signaling, which is responsible for the maintenance of optimal mitochondrial functioning, and mitochondria-derived ROS participate as signaling molecules in this process. Our results showed that in sAD patients cells, there is a shift in the balance of mitochondrial function, possibly in response to the presence of cellular stress related to disease development. MDPI 2021-06-10 /pmc/articles/PMC8229029/ /pubmed/34200581 http://dx.doi.org/10.3390/antiox10060938 Text en © 2021 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 Drabik, Karolina Malińska, Dominika Piecyk, Karolina Dębska-Vielhaber, Grażyna Vielhaber, Stefan Duszyński, Jerzy Szczepanowska, Joanna Effect of Chronic Stress Present in Fibroblasts Derived from Patients with a Sporadic Form of AD on Mitochondrial Function and Mitochondrial Turnover |
title | Effect of Chronic Stress Present in Fibroblasts Derived from Patients with a Sporadic Form of AD on Mitochondrial Function and Mitochondrial Turnover |
title_full | Effect of Chronic Stress Present in Fibroblasts Derived from Patients with a Sporadic Form of AD on Mitochondrial Function and Mitochondrial Turnover |
title_fullStr | Effect of Chronic Stress Present in Fibroblasts Derived from Patients with a Sporadic Form of AD on Mitochondrial Function and Mitochondrial Turnover |
title_full_unstemmed | Effect of Chronic Stress Present in Fibroblasts Derived from Patients with a Sporadic Form of AD on Mitochondrial Function and Mitochondrial Turnover |
title_short | Effect of Chronic Stress Present in Fibroblasts Derived from Patients with a Sporadic Form of AD on Mitochondrial Function and Mitochondrial Turnover |
title_sort | effect of chronic stress present in fibroblasts derived from patients with a sporadic form of ad on mitochondrial function and mitochondrial turnover |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229029/ https://www.ncbi.nlm.nih.gov/pubmed/34200581 http://dx.doi.org/10.3390/antiox10060938 |
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