ArticleCell death & disease2015
A bacterial metabolite induces glutathione-tractable proteostatic damage, proteasomal disturbances, and PINK1-dependent autophagy in C. elegans.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Gut microbiota and Parkinson's disease: exploring pathogenesis and potential therapeutic strategies from a gut-brain axis perspective.iScience · 2026Review
- Dopaminergic neurodegeneration inmicroPublication biology · 2025Article
- Epithelial UNC-23 limits mechanical stress to maintain glia-neuron architecture in C. elegans.Developmental cell · 2024Article
- Identification of the bacterial metabolite aerugine as potential trigger of human dopaminergic neurodegeneration.Environment international · 2023Article
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- UsingFrontiers in pharmacology · 2022Review
- Ubiquitin-related processes and innate immunity in C. elegans.Cellular and molecular life sciences : CMLS · 2021Review
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- Glycolate combats massive oxidative stress by restoring redox potential in Caenorhabditis elegans.Communications biology · 2021Article
- Innate immunity in C. elegans.Current topics in developmental biology · 2021Review
- Modeling neurodegeneration inDisease models & mechanisms · 2020Review
- Perfluorooctane Sulfonate (PFOS) Produces Dopaminergic Neuropathology in Caenorhabditis elegans.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- ApoE-associated modulation of neuroprotection from Aβ-mediated neurodegeneration in transgenicDisease models & mechanisms · 2019Article
- No Country for Old Worms: A Systematic Review of the Application ofMetabolites · 2018Review
- The Small GTPase RAC1/CED-10 Is Essential in Maintaining Dopaminergic Neuron Function and Survival Against α-Synuclein-Induced Toxicity.Molecular neurobiology · 2018Article
- Gene-by-environment interactions that disrupt mitochondrial homeostasis cause neurodegeneration in C. elegans Parkinson's models.Cell death & disease · 2018Article
- Modeling Parkinson's Disease in C. elegans.Journal of Parkinson's disease · 2018Review
- Activation of the mitochondrial unfolded protein response promotes longevity and dopamine neuron survival in Parkinson's disease models.Scientific reports · 2017Article
- Dysregulation of the Mitochondrial Unfolded Protein Response Induces Non-Apoptotic Dopaminergic Neurodegeneration inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Inhibition of cancer antioxidant defense by natural compounds.Oncotarget · 2017Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Gene-by-environment interactions are thought to underlie the majority of idiopathic cases of neurodegenerative disease. Recently, we reported that an environmental metabolite extracted from Streptomyces venezuelae increases ROS and damages mitochondria, leading to eventual neurodegeneration of C. elegans dopaminergic neurons. Here we link those data to idiopathic disease models that predict loss of protein handling as a component of disorder progression. We demonstrate that the bacterial metabolite leads to proteostatic disruption in multiple protein-misfolding models and has the potential to synergistically enhance the toxicity of aggregate-prone proteins. Genetically, this metabolite is epistatically regulated by loss-of-function to pink-1, the C. elegans PARK6 homolog responsible for mitochondrial maintenance and autophagy in other animal systems. In addition, the metabolite works through a genetic pathway analogous to loss-of-function in the ubiquitin proteasome system (UPS), which we find is also epistatically regulated by loss of PINK-1 homeostasis. To determine remitting counter agents, we investigated several established antioxidants and found that glutathione (GSH) can significantly protect against metabolite-induced proteostasis disruption. In addition, GSH protects against the toxicity of MG132 and can compensate for the combined loss of both pink-1 and the E3 ligase pdr-1, a Parkin homolog. In assessing the impact of this metabolite on mitochondrial maintenance, we observe that it causes fragmentation of mitochondria that is attenuated by GSH and an initial surge in PINK-1-dependent autophagy. These studies mechanistically advance our understanding of a putative environmental contributor to neurodegeneration and factors influencing in vivo neurotoxicity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.