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Lipid disequilibrium in biological membranes, a possible pathway to neurodegeneration
We recently reported that knocking down the enzyme phosphatidylserine decarboxylase, which synthesizes the phospholipid phosphatidylethanolamine (PE) in mitochondria, perturbs the homeostasis of the human Parkinson disease (PD) protein α-synuclein (expressed in yeast or worms). In yeast, low PE in t...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Taylor & Francis
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594524/ https://www.ncbi.nlm.nih.gov/pubmed/26480301 http://dx.doi.org/10.4161/19420889.2014.993266 |
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author | Witt, Stephan N. |
author_facet | Witt, Stephan N. |
author_sort | Witt, Stephan N. |
collection | PubMed |
description | We recently reported that knocking down the enzyme phosphatidylserine decarboxylase, which synthesizes the phospholipid phosphatidylethanolamine (PE) in mitochondria, perturbs the homeostasis of the human Parkinson disease (PD) protein α-synuclein (expressed in yeast or worms). In yeast, low PE in the psd1Δ deletion mutant induces α-synuclein to enter cytoplasmic foci, the level of this protein increases 3-fold compared to wild-type cells, and the mutant cells are severely sick. The metabolite ethanolamine protects both yeast and worms from the deleterious synergistic effects of low mitochondrial PE and α-synuclein. Here we highlight a Drosophila mutant called easily shocked—thought to be a model of epilepsy—that cannot use ethanolamine to synthesize PE. We also highlight recently identified mutated genes associated with defective lipid metabolism in PD and epilepsy patients. We propose that disruptions in lipid homeostasis (synthesis and degradation) may be responsible for some cases of PD and epilepsy. |
format | Online Article Text |
id | pubmed-4594524 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-45945242015-10-16 Lipid disequilibrium in biological membranes, a possible pathway to neurodegeneration Witt, Stephan N. Commun Integr Biol Article Addendum We recently reported that knocking down the enzyme phosphatidylserine decarboxylase, which synthesizes the phospholipid phosphatidylethanolamine (PE) in mitochondria, perturbs the homeostasis of the human Parkinson disease (PD) protein α-synuclein (expressed in yeast or worms). In yeast, low PE in the psd1Δ deletion mutant induces α-synuclein to enter cytoplasmic foci, the level of this protein increases 3-fold compared to wild-type cells, and the mutant cells are severely sick. The metabolite ethanolamine protects both yeast and worms from the deleterious synergistic effects of low mitochondrial PE and α-synuclein. Here we highlight a Drosophila mutant called easily shocked—thought to be a model of epilepsy—that cannot use ethanolamine to synthesize PE. We also highlight recently identified mutated genes associated with defective lipid metabolism in PD and epilepsy patients. We propose that disruptions in lipid homeostasis (synthesis and degradation) may be responsible for some cases of PD and epilepsy. Taylor & Francis 2015-01-08 /pmc/articles/PMC4594524/ /pubmed/26480301 http://dx.doi.org/10.4161/19420889.2014.993266 Text en © 2014 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. |
spellingShingle | Article Addendum Witt, Stephan N. Lipid disequilibrium in biological membranes, a possible pathway to neurodegeneration |
title | Lipid disequilibrium in biological membranes, a possible pathway to neurodegeneration |
title_full | Lipid disequilibrium in biological membranes, a possible pathway to neurodegeneration |
title_fullStr | Lipid disequilibrium in biological membranes, a possible pathway to neurodegeneration |
title_full_unstemmed | Lipid disequilibrium in biological membranes, a possible pathway to neurodegeneration |
title_short | Lipid disequilibrium in biological membranes, a possible pathway to neurodegeneration |
title_sort | lipid disequilibrium in biological membranes, a possible pathway to neurodegeneration |
topic | Article Addendum |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594524/ https://www.ncbi.nlm.nih.gov/pubmed/26480301 http://dx.doi.org/10.4161/19420889.2014.993266 |
work_keys_str_mv | AT wittstephann lipiddisequilibriuminbiologicalmembranesapossiblepathwaytoneurodegeneration |