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Antioxidants
Volume 14
Issue 6
10.3390/antiox14060693
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

The Biological Consequences of the Knockout of Genes Involved in the Synthesis and Metabolism of H2S in Drosophila melanogaster

by
Victoria Y. Shilova
1,
David G. Garbuz
1,
Lyubov N. Chuvakova
1,
Alexander P. Rezvykh
1,
Sergei Y. Funikov
1,
Artem I. Davletshin
1,
Svetlana Y. Sorokina
2,
Ekaterina A. Nikitina
3,4,
Olga Gorenskaya
1,5,
Michael B. Evgen’ev
1,6 and
Olga G. Zatsepina
1,*
1
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
2
Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 119334 Moscow, Russia
3
Pavlov Institute of Physiology, Russian Academy of Sciences, 199034 Saint-Petersburg, Russia
4
Herzen State Pedagogical University of Russia, Biology Department, 191186 Saint-Petersburg, Russia
5
Federal Scientific Center of Hygiene Named After F.F. Erisman of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, 141014 Mytishchi, Russia
6
Institute of Evolution, University of Haifa, Haifa 3498838, Israel
*
Author to whom correspondence should be addressed.
Antioxidants 2025, 14(6), 693; https://doi.org/10.3390/antiox14060693
Submission received: 27 March 2025 / Revised: 30 May 2025 / Accepted: 3 June 2025 / Published: 6 June 2025
(This article belongs to the Section Antioxidant Enzyme Systems)
Versions Notes

Abstract

Here, we describe the effects of double knockout (KO) of the cbs and cse genes, which are responsible for H2S synthesis through the transsulfuration pathway, and KO of the sulfurtransferase gene (dtst1) in Drosophila melanogaster females. The analysis of H2S production in flies showed minimal levels in the double- and triple-knockout strains. The double- (cbs-/-; cse-/-) and triple- (cbs-/-; cse-/-; dtst-/-) KO flies exhibited a shortened lifespan and reduced fecundity, and showed dramatic changes in Malpighian tubule morphology. The transcriptomic analysis revealed a profound increase in the expression levels of several genes involved in excretory system function in the double-KO and especially the triple-KO flies. Importantly, major groups of differentially expressed genes (DEGs) in the whole bodies of females and ovaries of KO strains included genes responsible for detoxification, reproduction, mitochondrial activity, excretion, cell migration, and muscle system function. The reduced fecundity observed in the double- and triple-KO flies correlated with pronounced changes in the ovarian transcriptome. At the same time, the single knockout of dtst1 increased the flies’ fecundity and lifespan. Our experiments exploring unique Drosophila strains with KO of major H2S-related genes revealed several new pathways controlled by this ancient adaptogenic system that is involved in various human diseases and aging.
Keywords: Drosophila melanogaster; knockout (KO) strains; cystathionine-β-synthase; cystathionine γ-lyase; sulfurtransferase; life-history traits Drosophila melanogaster; knockout (KO) strains; cystathionine-β-synthase; cystathionine γ-lyase; sulfurtransferase; life-history traits

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MDPI and ACS Style

Shilova, V.Y.; Garbuz, D.G.; Chuvakova, L.N.; Rezvykh, A.P.; Funikov, S.Y.; Davletshin, A.I.; Sorokina, S.Y.; Nikitina, E.A.; Gorenskaya, O.; Evgen’ev, M.B.; et al. The Biological Consequences of the Knockout of Genes Involved in the Synthesis and Metabolism of H2S in Drosophila melanogaster. Antioxidants 2025, 14, 693. https://doi.org/10.3390/antiox14060693

AMA Style

Shilova VY, Garbuz DG, Chuvakova LN, Rezvykh AP, Funikov SY, Davletshin AI, Sorokina SY, Nikitina EA, Gorenskaya O, Evgen’ev MB, et al. The Biological Consequences of the Knockout of Genes Involved in the Synthesis and Metabolism of H2S in Drosophila melanogaster. Antioxidants. 2025; 14(6):693. https://doi.org/10.3390/antiox14060693

Chicago/Turabian Style

Shilova, Victoria Y., David G. Garbuz, Lyubov N. Chuvakova, Alexander P. Rezvykh, Sergei Y. Funikov, Artem I. Davletshin, Svetlana Y. Sorokina, Ekaterina A. Nikitina, Olga Gorenskaya, Michael B. Evgen’ev, and et al. 2025. "The Biological Consequences of the Knockout of Genes Involved in the Synthesis and Metabolism of H2S in Drosophila melanogaster" Antioxidants 14, no. 6: 693. https://doi.org/10.3390/antiox14060693

APA Style

Shilova, V. Y., Garbuz, D. G., Chuvakova, L. N., Rezvykh, A. P., Funikov, S. Y., Davletshin, A. I., Sorokina, S. Y., Nikitina, E. A., Gorenskaya, O., Evgen’ev, M. B., & Zatsepina, O. G. (2025). The Biological Consequences of the Knockout of Genes Involved in the Synthesis and Metabolism of H2S in Drosophila melanogaster. Antioxidants, 14(6), 693. https://doi.org/10.3390/antiox14060693

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