Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies
Large-scale insecticide application is a primary weapon in the control of insect pests in agriculture. However, a growing body of evidence indicates that it is contributing to the global decline in population sizes of many beneficial insect species. Spinosad emerged as an organic alternative to synt...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/73812 |
| _version_ | 1818026385761894400 |
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| author | Felipe Martelli Natalia H Hernandes Zhongyuan Zuo Julia Wang Ching-On Wong Nicholas E Karagas Ute Roessner Thusita Rupasinghe Charles Robin Kartik Venkatachalam Trent Perry Philip Batterham Hugo J Bellen |
| author_facet | Felipe Martelli Natalia H Hernandes Zhongyuan Zuo Julia Wang Ching-On Wong Nicholas E Karagas Ute Roessner Thusita Rupasinghe Charles Robin Kartik Venkatachalam Trent Perry Philip Batterham Hugo J Bellen |
| author_sort | Felipe Martelli |
| collection | DOAJ |
| description | Large-scale insecticide application is a primary weapon in the control of insect pests in agriculture. However, a growing body of evidence indicates that it is contributing to the global decline in population sizes of many beneficial insect species. Spinosad emerged as an organic alternative to synthetic insecticides and is considered less harmful to beneficial insects, yet its mode of action remains unclear. Using Drosophila, we show that low doses of spinosad antagonize its neuronal target, the nicotinic acetylcholine receptor subunit alpha 6 (nAChRα6), reducing the cholinergic response. We show that the nAChRα6 receptors are transported to lysosomes that become enlarged and increase in number upon low doses of spinosad treatment. Lysosomal dysfunction is associated with mitochondrial stress and elevated levels of reactive oxygen species (ROS) in the central nervous system where nAChRα6 is broadly expressed. ROS disturb lipid storage in metabolic tissues in an nAChRα6-dependent manner. Spinosad toxicity is ameliorated with the antioxidant N-acetylcysteine amide. Chronic exposure of adult virgin females to low doses of spinosad leads to mitochondrial defects, severe neurodegeneration, and blindness. These deleterious effects of low-dose exposures warrant rigorous investigation of its impacts on beneficial insects. |
| first_indexed | 2024-12-10T04:31:10Z |
| format | Article |
| id | doaj.art-51846748db3143c4a3631663c675f04a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:31:10Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-51846748db3143c4a3631663c675f04a2022-12-22T02:02:09ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.73812Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in fliesFelipe Martelli0https://orcid.org/0000-0003-4783-9025Natalia H Hernandes1https://orcid.org/0000-0001-5644-6974Zhongyuan Zuo2Julia Wang3Ching-On Wong4Nicholas E Karagas5Ute Roessner6Thusita Rupasinghe7Charles Robin8Kartik Venkatachalam9https://orcid.org/0000-0002-3055-9265Trent Perry10https://orcid.org/0000-0002-8045-0487Philip Batterham11https://orcid.org/0000-0001-9840-9119Hugo J Bellen12https://orcid.org/0000-0001-5992-5989School of BioSciences, The University of Melbourne, Melbourne, AustraliaSchool of BioSciences, The University of Melbourne, Melbourne, AustraliaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United StatesDepartment of Integrative Biology and Pharmacology, McGovern Medical School at the University of Texas Health Sciences Center, Houston, United StatesDepartment of Integrative Biology and Pharmacology, McGovern Medical School at the University of Texas Health Sciences Center, Houston, United StatesSchool of BioSciences, The University of Melbourne, Melbourne, AustraliaSchool of BioSciences, The University of Melbourne, Melbourne, AustraliaSchool of BioSciences, The University of Melbourne, Melbourne, AustraliaDepartment of Integrative Biology and Pharmacology, McGovern Medical School at the University of Texas Health Sciences Center, Houston, United StatesSchool of BioSciences, The University of Melbourne, Melbourne, AustraliaSchool of BioSciences, The University of Melbourne, Melbourne, AustraliaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States; Neurological Research Institute, Texas Children Hospital, Houston, United States; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United StatesLarge-scale insecticide application is a primary weapon in the control of insect pests in agriculture. However, a growing body of evidence indicates that it is contributing to the global decline in population sizes of many beneficial insect species. Spinosad emerged as an organic alternative to synthetic insecticides and is considered less harmful to beneficial insects, yet its mode of action remains unclear. Using Drosophila, we show that low doses of spinosad antagonize its neuronal target, the nicotinic acetylcholine receptor subunit alpha 6 (nAChRα6), reducing the cholinergic response. We show that the nAChRα6 receptors are transported to lysosomes that become enlarged and increase in number upon low doses of spinosad treatment. Lysosomal dysfunction is associated with mitochondrial stress and elevated levels of reactive oxygen species (ROS) in the central nervous system where nAChRα6 is broadly expressed. ROS disturb lipid storage in metabolic tissues in an nAChRα6-dependent manner. Spinosad toxicity is ameliorated with the antioxidant N-acetylcysteine amide. Chronic exposure of adult virgin females to low doses of spinosad leads to mitochondrial defects, severe neurodegeneration, and blindness. These deleterious effects of low-dose exposures warrant rigorous investigation of its impacts on beneficial insects.https://elifesciences.org/articles/73812spinosadoxidative stresslipid dysregulationneurodegenerationantioxidantlysosomal dysfunction |
| spellingShingle | Felipe Martelli Natalia H Hernandes Zhongyuan Zuo Julia Wang Ching-On Wong Nicholas E Karagas Ute Roessner Thusita Rupasinghe Charles Robin Kartik Venkatachalam Trent Perry Philip Batterham Hugo J Bellen Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies eLife spinosad oxidative stress lipid dysregulation neurodegeneration antioxidant lysosomal dysfunction |
| title | Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies |
| title_full | Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies |
| title_fullStr | Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies |
| title_full_unstemmed | Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies |
| title_short | Low doses of the organic insecticide spinosad trigger lysosomal defects, elevated ROS, lipid dysregulation, and neurodegeneration in flies |
| title_sort | low doses of the organic insecticide spinosad trigger lysosomal defects elevated ros lipid dysregulation and neurodegeneration in flies |
| topic | spinosad oxidative stress lipid dysregulation neurodegeneration antioxidant lysosomal dysfunction |
| url | https://elifesciences.org/articles/73812 |
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