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The Effects of PP2A Disruption on ER-Mitochondria Contact and Mitochondrial Functions in Neuronal-like Cells

Mitochondria-associated membranes (MAMs) regulate several cellular processes, including calcium homeostasis and mitochondrial function, and dynamics. While MAMs are upregulated in Alzheimer’s disease (AD), the mechanisms underlying this increase remain unknown. A possible mechanism may include dysre...

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Autores principales: Chaiwijit, Phaewa, Uppakara, Kwanchanok, Asavapanumas, Nithi, Saengsawang, Witchuda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135475/
https://www.ncbi.nlm.nih.gov/pubmed/37189629
http://dx.doi.org/10.3390/biomedicines11041011
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author Chaiwijit, Phaewa
Uppakara, Kwanchanok
Asavapanumas, Nithi
Saengsawang, Witchuda
author_facet Chaiwijit, Phaewa
Uppakara, Kwanchanok
Asavapanumas, Nithi
Saengsawang, Witchuda
author_sort Chaiwijit, Phaewa
collection PubMed
description Mitochondria-associated membranes (MAMs) regulate several cellular processes, including calcium homeostasis and mitochondrial function, and dynamics. While MAMs are upregulated in Alzheimer’s disease (AD), the mechanisms underlying this increase remain unknown. A possible mechanism may include dysregulation of protein phosphatase 2A (PP2A), which is reduced in the AD brain. Furthermore, PP2A has been previously reported to modulate MAM formation in hepatocytes. However, it is unknown whether PP2A and MAMs are linked in neuronal cells. Here, to test the correlation between PP2A and MAMs, we inhibited the activity of PP2A to mimic its low levels in AD brains and observed MAM formation, function, and dynamics. MAMs were significantly increased after PP2A inhibition, which correlated with elevated mitochondrial Ca(2+) influx and disrupted mitochondrial membrane potential and mitochondrial fission. This study highlights the essential role PP2A plays in regulating MAM formation and mitochondrial function and dynamics for the first time in neuronal-like cells.
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spelling pubmed-101354752023-04-28 The Effects of PP2A Disruption on ER-Mitochondria Contact and Mitochondrial Functions in Neuronal-like Cells Chaiwijit, Phaewa Uppakara, Kwanchanok Asavapanumas, Nithi Saengsawang, Witchuda Biomedicines Article Mitochondria-associated membranes (MAMs) regulate several cellular processes, including calcium homeostasis and mitochondrial function, and dynamics. While MAMs are upregulated in Alzheimer’s disease (AD), the mechanisms underlying this increase remain unknown. A possible mechanism may include dysregulation of protein phosphatase 2A (PP2A), which is reduced in the AD brain. Furthermore, PP2A has been previously reported to modulate MAM formation in hepatocytes. However, it is unknown whether PP2A and MAMs are linked in neuronal cells. Here, to test the correlation between PP2A and MAMs, we inhibited the activity of PP2A to mimic its low levels in AD brains and observed MAM formation, function, and dynamics. MAMs were significantly increased after PP2A inhibition, which correlated with elevated mitochondrial Ca(2+) influx and disrupted mitochondrial membrane potential and mitochondrial fission. This study highlights the essential role PP2A plays in regulating MAM formation and mitochondrial function and dynamics for the first time in neuronal-like cells. MDPI 2023-03-26 /pmc/articles/PMC10135475/ /pubmed/37189629 http://dx.doi.org/10.3390/biomedicines11041011 Text en © 2023 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
Chaiwijit, Phaewa
Uppakara, Kwanchanok
Asavapanumas, Nithi
Saengsawang, Witchuda
The Effects of PP2A Disruption on ER-Mitochondria Contact and Mitochondrial Functions in Neuronal-like Cells
title The Effects of PP2A Disruption on ER-Mitochondria Contact and Mitochondrial Functions in Neuronal-like Cells
title_full The Effects of PP2A Disruption on ER-Mitochondria Contact and Mitochondrial Functions in Neuronal-like Cells
title_fullStr The Effects of PP2A Disruption on ER-Mitochondria Contact and Mitochondrial Functions in Neuronal-like Cells
title_full_unstemmed The Effects of PP2A Disruption on ER-Mitochondria Contact and Mitochondrial Functions in Neuronal-like Cells
title_short The Effects of PP2A Disruption on ER-Mitochondria Contact and Mitochondrial Functions in Neuronal-like Cells
title_sort effects of pp2a disruption on er-mitochondria contact and mitochondrial functions in neuronal-like cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10135475/
https://www.ncbi.nlm.nih.gov/pubmed/37189629
http://dx.doi.org/10.3390/biomedicines11041011
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