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Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae
The Drosophila bang-sensitive mutant tko(25t), manifesting a global deficiency in oxidative phosphorylation due to a mitochondrial protein synthesis defect, exhibits a pronounced delay in larval development. We previously identified a number of metabolic abnormalities in tko(25t) larvae, including e...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988875/ https://www.ncbi.nlm.nih.gov/pubmed/31526131 http://dx.doi.org/10.1080/19336934.2019.1662266 |
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author | George, Jack Tuomela, Tea Kemppainen, Esko Nurminen, Antti Braun, Samuel Yalgin, Cagri Jacobs, Howard T. |
author_facet | George, Jack Tuomela, Tea Kemppainen, Esko Nurminen, Antti Braun, Samuel Yalgin, Cagri Jacobs, Howard T. |
author_sort | George, Jack |
collection | PubMed |
description | The Drosophila bang-sensitive mutant tko(25t), manifesting a global deficiency in oxidative phosphorylation due to a mitochondrial protein synthesis defect, exhibits a pronounced delay in larval development. We previously identified a number of metabolic abnormalities in tko(25t) larvae, including elevated pyruvate and lactate, and found the larval gut to be a crucial tissue for the regulation of larval growth in the mutant. Here we established that expression of wild-type tko in any of several other tissues of tko(25t) also partially alleviates developmental delay. The effects appeared to be additive, whilst knockdown of tko in a variety of specific tissues phenocopied tko(25t), producing developmental delay and bang-sensitivity. These findings imply the existence of a systemic signal regulating growth in response to mitochondrial dysfunction. Drugs and RNAi-targeted on pyruvate metabolism interacted with tko(25t) in ways that implicated pyruvate or one of its metabolic derivatives in playing a central role in generating such a signal. RNA-seq revealed that dietary pyruvate-induced changes in transcript representation were mostly non-coherent with those produced by tko(25t) or high-sugar, consistent with the idea that growth regulation operates primarily at the translational and/or metabolic level. |
format | Online Article Text |
id | pubmed-6988875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-69888752020-02-14 Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae George, Jack Tuomela, Tea Kemppainen, Esko Nurminen, Antti Braun, Samuel Yalgin, Cagri Jacobs, Howard T. Fly (Austin) Research Paper The Drosophila bang-sensitive mutant tko(25t), manifesting a global deficiency in oxidative phosphorylation due to a mitochondrial protein synthesis defect, exhibits a pronounced delay in larval development. We previously identified a number of metabolic abnormalities in tko(25t) larvae, including elevated pyruvate and lactate, and found the larval gut to be a crucial tissue for the regulation of larval growth in the mutant. Here we established that expression of wild-type tko in any of several other tissues of tko(25t) also partially alleviates developmental delay. The effects appeared to be additive, whilst knockdown of tko in a variety of specific tissues phenocopied tko(25t), producing developmental delay and bang-sensitivity. These findings imply the existence of a systemic signal regulating growth in response to mitochondrial dysfunction. Drugs and RNAi-targeted on pyruvate metabolism interacted with tko(25t) in ways that implicated pyruvate or one of its metabolic derivatives in playing a central role in generating such a signal. RNA-seq revealed that dietary pyruvate-induced changes in transcript representation were mostly non-coherent with those produced by tko(25t) or high-sugar, consistent with the idea that growth regulation operates primarily at the translational and/or metabolic level. Taylor & Francis 2019-09-17 /pmc/articles/PMC6988875/ /pubmed/31526131 http://dx.doi.org/10.1080/19336934.2019.1662266 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Research Paper George, Jack Tuomela, Tea Kemppainen, Esko Nurminen, Antti Braun, Samuel Yalgin, Cagri Jacobs, Howard T. Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae |
title | Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae |
title_full | Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae |
title_fullStr | Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae |
title_full_unstemmed | Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae |
title_short | Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae |
title_sort | mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in drosophila larvae |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988875/ https://www.ncbi.nlm.nih.gov/pubmed/31526131 http://dx.doi.org/10.1080/19336934.2019.1662266 |
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