Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae
The Drosophila bang-sensitive mutant tko25t, 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 tko25t larvae, including eleva...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-10-01
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| Series: | Fly |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/19336934.2019.1662266 |
| _version_ | 1797678374128189440 |
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| author | Jack George Tea Tuomela Esko Kemppainen Antti Nurminen Samuel Braun Cagri Yalgin Howard T. Jacobs |
| author_facet | Jack George Tea Tuomela Esko Kemppainen Antti Nurminen Samuel Braun Cagri Yalgin Howard T. Jacobs |
| author_sort | Jack George |
| collection | DOAJ |
| description | The Drosophila bang-sensitive mutant tko25t, 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 tko25t 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 tko25t also partially alleviates developmental delay. The effects appeared to be additive, whilst knockdown of tko in a variety of specific tissues phenocopied tko25t, 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 tko25t 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 tko25t or high-sugar, consistent with the idea that growth regulation operates primarily at the translational and/or metabolic level. |
| first_indexed | 2024-03-11T22:58:48Z |
| format | Article |
| id | doaj.art-95f7a6c5ad4842c49eb40e9a42c0080d |
| institution | Directory Open Access Journal |
| issn | 1933-6934 1933-6942 |
| language | English |
| last_indexed | 2024-03-11T22:58:48Z |
| publishDate | 2019-10-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Fly |
| spelling | doaj.art-95f7a6c5ad4842c49eb40e9a42c0080d2023-09-21T15:09:08ZengTaylor & Francis GroupFly1933-69341933-69422019-10-01131-4122810.1080/19336934.2019.16622661662266Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvaeJack George0Tea Tuomela1Esko Kemppainen2Antti Nurminen3Samuel Braun4Cagri Yalgin5Howard T. Jacobs6Tampere UniversityTampere UniversityTampere UniversityTampere UniversityTampere UniversityTampere UniversityTampere UniversityThe Drosophila bang-sensitive mutant tko25t, 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 tko25t 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 tko25t also partially alleviates developmental delay. The effects appeared to be additive, whilst knockdown of tko in a variety of specific tissues phenocopied tko25t, 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 tko25t 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 tko25t or high-sugar, consistent with the idea that growth regulation operates primarily at the translational and/or metabolic level.http://dx.doi.org/10.1080/19336934.2019.1662266mitochondriaprotein synthesislactic acidosisrespirationtranslationlarva |
| spellingShingle | Jack George Tea Tuomela Esko Kemppainen Antti Nurminen Samuel Braun Cagri Yalgin Howard T. Jacobs Mitochondrial dysfunction generates a growth-restraining signal linked to pyruvate in Drosophila larvae Fly mitochondria protein synthesis lactic acidosis respiration translation larva |
| 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 | mitochondria protein synthesis lactic acidosis respiration translation larva |
| url | http://dx.doi.org/10.1080/19336934.2019.1662266 |
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