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Mutants for Drosophila Isocitrate Dehydrogenase 3b Are Defective in Mitochondrial Function and Larval Cell Death

The death of larval salivary gland cells during metamorphosis in Drosophila melanogaster has been a key system for studying steroid controlled programmed cell death. This death is induced by a pulse of the steroid hormone ecdysone that takes place at the end of the prepupal period. For many years, i...

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Autores principales: Duncan, Dianne M., Kiefel, Paula, Duncan, Ian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Genetics Society of America 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345709/
https://www.ncbi.nlm.nih.gov/pubmed/28104670
http://dx.doi.org/10.1534/g3.116.037366
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author Duncan, Dianne M.
Kiefel, Paula
Duncan, Ian
author_facet Duncan, Dianne M.
Kiefel, Paula
Duncan, Ian
author_sort Duncan, Dianne M.
collection PubMed
description The death of larval salivary gland cells during metamorphosis in Drosophila melanogaster has been a key system for studying steroid controlled programmed cell death. This death is induced by a pulse of the steroid hormone ecdysone that takes place at the end of the prepupal period. For many years, it has been thought that the ecdysone direct response gene Eip93F (E93) plays a critical role in initiating salivary gland cell death. This conclusion was based largely on the finding that the three “type” alleles of E93 cause a near-complete block in salivary gland cell death. Here, we show that these three mutations are in fact allelic to Idh3b, a nearby gene that encodes the β subunit of isocitrate dehydrogenase 3, a mitochondrial enzyme of the tricarboxylic acid (TCA) cycle. The strongest of the Idh3b alleles appears to cause a near-complete block in oxidative phosphorylation, as mitochondria are depolarized in mutant larvae, and development arrests early during cleavage in embryos from homozygous-mutant germline mothers. Idh3b-mutant larval salivary gland cells fail to undergo mitochondrial fragmentation, which normally precedes the death of these cells, and do not initiate autophagy, an early step in the cell death program. These observations suggest a close relationship between the TCA cycle and the initiation of larval cell death. In normal development, tagged Idh3b is released from salivary gland mitochondria during their fragmentation, suggesting that Idh3b may be an apoptogenic factor that functions much like released cytochrome c in mammalian cells.
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spelling pubmed-53457092017-03-21 Mutants for Drosophila Isocitrate Dehydrogenase 3b Are Defective in Mitochondrial Function and Larval Cell Death Duncan, Dianne M. Kiefel, Paula Duncan, Ian G3 (Bethesda) Investigations The death of larval salivary gland cells during metamorphosis in Drosophila melanogaster has been a key system for studying steroid controlled programmed cell death. This death is induced by a pulse of the steroid hormone ecdysone that takes place at the end of the prepupal period. For many years, it has been thought that the ecdysone direct response gene Eip93F (E93) plays a critical role in initiating salivary gland cell death. This conclusion was based largely on the finding that the three “type” alleles of E93 cause a near-complete block in salivary gland cell death. Here, we show that these three mutations are in fact allelic to Idh3b, a nearby gene that encodes the β subunit of isocitrate dehydrogenase 3, a mitochondrial enzyme of the tricarboxylic acid (TCA) cycle. The strongest of the Idh3b alleles appears to cause a near-complete block in oxidative phosphorylation, as mitochondria are depolarized in mutant larvae, and development arrests early during cleavage in embryos from homozygous-mutant germline mothers. Idh3b-mutant larval salivary gland cells fail to undergo mitochondrial fragmentation, which normally precedes the death of these cells, and do not initiate autophagy, an early step in the cell death program. These observations suggest a close relationship between the TCA cycle and the initiation of larval cell death. In normal development, tagged Idh3b is released from salivary gland mitochondria during their fragmentation, suggesting that Idh3b may be an apoptogenic factor that functions much like released cytochrome c in mammalian cells. Genetics Society of America 2017-01-17 /pmc/articles/PMC5345709/ /pubmed/28104670 http://dx.doi.org/10.1534/g3.116.037366 Text en Copyright © 2017 Duncan et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigations
Duncan, Dianne M.
Kiefel, Paula
Duncan, Ian
Mutants for Drosophila Isocitrate Dehydrogenase 3b Are Defective in Mitochondrial Function and Larval Cell Death
title Mutants for Drosophila Isocitrate Dehydrogenase 3b Are Defective in Mitochondrial Function and Larval Cell Death
title_full Mutants for Drosophila Isocitrate Dehydrogenase 3b Are Defective in Mitochondrial Function and Larval Cell Death
title_fullStr Mutants for Drosophila Isocitrate Dehydrogenase 3b Are Defective in Mitochondrial Function and Larval Cell Death
title_full_unstemmed Mutants for Drosophila Isocitrate Dehydrogenase 3b Are Defective in Mitochondrial Function and Larval Cell Death
title_short Mutants for Drosophila Isocitrate Dehydrogenase 3b Are Defective in Mitochondrial Function and Larval Cell Death
title_sort mutants for drosophila isocitrate dehydrogenase 3b are defective in mitochondrial function and larval cell death
topic Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345709/
https://www.ncbi.nlm.nih.gov/pubmed/28104670
http://dx.doi.org/10.1534/g3.116.037366
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