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Conditional targeting of phosphatidylserine decarboxylase to lipid droplets
Phosphatidylethanolamine is an abundant component of most cellular membranes whose physical and chemical properties modulate multiple aspects of organelle membrane dynamics. An evolutionarily ancient mechanism for producing phosphatidylethanolamine is to decarboxylate phosphatidylserine and the enzy...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938800/ https://www.ncbi.nlm.nih.gov/pubmed/33593792 http://dx.doi.org/10.1242/bio.058516 |
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author | Kumar, Santosh Chitraju, Chandramohan Farese, Robert V. Walther, Tobias C. Burd, Christopher G. |
author_facet | Kumar, Santosh Chitraju, Chandramohan Farese, Robert V. Walther, Tobias C. Burd, Christopher G. |
author_sort | Kumar, Santosh |
collection | PubMed |
description | Phosphatidylethanolamine is an abundant component of most cellular membranes whose physical and chemical properties modulate multiple aspects of organelle membrane dynamics. An evolutionarily ancient mechanism for producing phosphatidylethanolamine is to decarboxylate phosphatidylserine and the enzyme catalyzing this reaction, phosphatidylserine decarboxylase, localizes to the inner membrane of the mitochondrion. We characterize a second form of phosphatidylserine decarboxylase, termed PISD-LD, that is generated by alternative splicing of PISD pre-mRNA and localizes to lipid droplets and to mitochondria. Sub-cellular targeting is controlled by a common segment of PISD-LD that is distinct from the catalytic domain and is regulated by nutritional state. Growth conditions that promote neutral lipid storage in lipid droplets favors targeting to lipid droplets, while targeting to mitochondria is favored by conditions that promote consumption of lipid droplets. Depletion of both forms of phosphatidylserine decarboxylase impairs triacylglycerol synthesis when cells are challenged with free fatty acid, indicating a crucial role phosphatidylserine decarboxylase in neutral lipid storage. The results reveal a previously unappreciated role for phosphatidylserine decarboxylase in lipid droplet biogenesis. |
format | Online Article Text |
id | pubmed-7938800 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-79388002021-03-08 Conditional targeting of phosphatidylserine decarboxylase to lipid droplets Kumar, Santosh Chitraju, Chandramohan Farese, Robert V. Walther, Tobias C. Burd, Christopher G. Biol Open Research Article Phosphatidylethanolamine is an abundant component of most cellular membranes whose physical and chemical properties modulate multiple aspects of organelle membrane dynamics. An evolutionarily ancient mechanism for producing phosphatidylethanolamine is to decarboxylate phosphatidylserine and the enzyme catalyzing this reaction, phosphatidylserine decarboxylase, localizes to the inner membrane of the mitochondrion. We characterize a second form of phosphatidylserine decarboxylase, termed PISD-LD, that is generated by alternative splicing of PISD pre-mRNA and localizes to lipid droplets and to mitochondria. Sub-cellular targeting is controlled by a common segment of PISD-LD that is distinct from the catalytic domain and is regulated by nutritional state. Growth conditions that promote neutral lipid storage in lipid droplets favors targeting to lipid droplets, while targeting to mitochondria is favored by conditions that promote consumption of lipid droplets. Depletion of both forms of phosphatidylserine decarboxylase impairs triacylglycerol synthesis when cells are challenged with free fatty acid, indicating a crucial role phosphatidylserine decarboxylase in neutral lipid storage. The results reveal a previously unappreciated role for phosphatidylserine decarboxylase in lipid droplet biogenesis. The Company of Biologists Ltd 2021-03-03 /pmc/articles/PMC7938800/ /pubmed/33593792 http://dx.doi.org/10.1242/bio.058516 Text en © 2021. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Kumar, Santosh Chitraju, Chandramohan Farese, Robert V. Walther, Tobias C. Burd, Christopher G. Conditional targeting of phosphatidylserine decarboxylase to lipid droplets |
title | Conditional targeting of phosphatidylserine decarboxylase to lipid droplets |
title_full | Conditional targeting of phosphatidylserine decarboxylase to lipid droplets |
title_fullStr | Conditional targeting of phosphatidylserine decarboxylase to lipid droplets |
title_full_unstemmed | Conditional targeting of phosphatidylserine decarboxylase to lipid droplets |
title_short | Conditional targeting of phosphatidylserine decarboxylase to lipid droplets |
title_sort | conditional targeting of phosphatidylserine decarboxylase to lipid droplets |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938800/ https://www.ncbi.nlm.nih.gov/pubmed/33593792 http://dx.doi.org/10.1242/bio.058516 |
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