Detection of Mitochondrial Toxicity of Environmental Pollutants Using<i>Caenorhabditis elegans</i>

Maurer, Laura L.; Luz, Anthony L.; Meyer, Joel N.

doi:10.1002/9781119329725.ch43

Cited by 8 publications

(6 citation statements)

References 394 publications

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“…elegans is an established toxicity model, showing strong prediction of toxicity for mammalian and other metazoan species. , C. elegans is also an excellent model for whole-organism high-throughput-based studies and has a highly conserved mitochondrial biology, , allowing the investigation of mitochondrial effects of toxicants more rapidly and thoroughly, compared to other animal models. These characteristics and many others make C.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Effects of Silver Nanoparticles on Development, Behavior, and Mitochondrial Function are Altered by Genetic Defects in Mitochondrial Dynamics

Mello

Maurer

Ryde

et al. 2022

Environ. Sci. Technol.

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Silver nanoparticles (AgNPs) are extensively used in consumer products and biomedical applications, thus guaranteeing both environmental and human exposures. Despite extensive research addressing AgNP safety, there are still major knowledge gaps regarding AgNP toxicity mechanisms, particularly in whole organisms. Mitochondrial dysfunction is frequently described as an important cytotoxicity mechanism for AgNPs; however, it is still unclear if mitochondria are the direct targets of AgNPs. To test this, we exposed the nematodeCaenorhabditis elegans to sublethal concentrations of AgNPs and assessed specific mitochondrial parameters as well as organismal-level endpoints that are highly reliant on mitochondrial function, such as development and chemotaxis behavior. All AgNPs tested significantly delayed nematode development, disrupted mitochondrial bioenergetics, and blocked chemotaxis. However, silver was not preferentially accumulated in mitochondria, indicating that these effects are likely not due to direct mitochondria–AgNP interactions. Mutant nematodes with deficiencies in mitochondrial dynamics displayed both greater and decreased susceptibility to AgNPs compared to wild-type nematodes, which was dependent on the assay and AgNP type. Our study suggests that AgNPs indirectly promote mitochondrial dysfunction, leading to adverse outcomes at the organismal level, and reveals a role of gene–environment interactions in the susceptibility to AgNPs. Finally, we propose a novel hypothetical adverse outcome pathway for AgNP effects to guide future research.

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Section: Introductionmentioning

confidence: 99%

In Vivo Effects of Silver Nanoparticles on Development, Behavior, and Mitochondrial Function are Altered by Genetic Defects in Mitochondrial Dynamics

Mello

Maurer

Ryde

et al. 2022

Environ. Sci. Technol.

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“…Recently, these have included medium-throughput analysis of small alternative animal models; in particular, the nematode C. elegans and zebrafish ( Danio rerio ) are among the most promising. Both have been used in medium-throughput assays ( Andreux et al , 2014 ; Bestman et al , 2015 ; Jayasundara et al , 2015 ; Luz et al , 2015 ; Maurer et al , 2018 ), and both have been successfully used in studies that identified late-life consequences of mitochondrial dysfunction ( Gonzalez-Hunt et al , 2014 ; Luz et al , 2017 ; Pinho et al , 2013 ). However, the complexity of whole organisms can sometimes limit interpretation and inferences about mechanisms of toxicity ( Brand and Nicholls, 2011 ).…”

Section: Cutting-edge Areas Of Researchmentioning

confidence: 99%

Mitochondrial Toxicity

Meyer

Hartman

Mello

2018

Toxicological Sciences

135

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Recent decades have seen a rapid increase in reported toxic effects of drugs and pollutants on mitochondria. Researchers have also documented many genetic differences leading to mitochondrial diseases, currently reported to affect ∼1 person in 4,300, creating a large number of potential gene-environment interactions in mitochondrial toxicity. We briefly review this history, and then highlight cutting-edge areas of mitochondrial research including the role of mitochondrial reactive oxygen species in signaling; increased understanding of fundamental biological processes involved in mitochondrial homeostasis (DNA maintenance and mutagenesis, mitochondrial stress response pathways, fusion and fission, autophagy and biogenesis, and exocytosis); systemic effects resulting from mitochondrial stresses in specific cell types; mitochondrial involvement in immune function; the growing evidence of long-term effects of mitochondrial toxicity; mitochondrial-epigenetic cross-talk; and newer approaches to test chemicals for mitochondrial toxicity. We also discuss the potential importance of hormetic effects of mitochondrial stressors. Finally, we comment on future areas of research we consider critical for mitochondrial toxicology, including increased integration of clinical, experimental laboratory, and epidemiological (human and wildlife) studies; improved understanding of biomarkers in the human population; and incorporation of other factors that affect mitochondria, such as diet, exercise, age, and nonchemical stressors.

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“…However, as for all model organisms, there are a variety of limitations; in the case of C. elegans , many are the inherent counterparts of the simplicity that makes the worm a powerful model. We recently reviewed genetic, biochemical and physiological differences between the worm and mammals relevant to toxicity (Maurer et al, )—here, we will highlight a few key differences. Perhaps most obviously, C. elegans lack many of the anatomical features of mammals, from cell types such as blood cells to organ systems such as lungs.…”

Section: Caenorhabditis Elegans As a Model System In Environmental Tomentioning

confidence: 99%

“…Richard Nass established the use of C. elegans for chemical-induced neurodegeneration (Nass et al, 2001(Nass et al, , 2002. The number of groups doing such work has grown rapidly in recent years, and C. elegans is now a well-characterized model for human and ecological toxicity and genotoxicity studies (Leung et al, 2008;Steinberg et al, 2008;Boyd et al, 2010;Helmcke et al, 2010;Allard et al, 2013;Choi et al, 2014;Meyer and Williams 2014;Ferreira and Allard 2015;Tejeda-Benitez and Olivero-Verbel 2016;Honnen 2017;Hunt 2017;Lenz et al, 2017;Maurer et al, 2017).…”

Section: Caenorhabditis Elegans As a Model System In Environmental Tomentioning

confidence: 99%

Caenorhabditis elegans as an emerging model system in environmental epigenetics

Weinhouse

Truong

Meyer

et al. 2018

Environ and Mol Mutagen

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The roundworm Caenorhabitis elegans has been an established model organism for the study of genetics and developmental biology, including studies of transcriptional regulation, since the 1970s. This model organism has continued to be used as a classical model system as the field of transcriptional regulation has expanded to include scientific advances in epigenetics and chromatin biology. In the last several decades, C. elegans has emerged as a powerful model for environmental toxicology, particularly for the study of chemical genotoxicity. Here, we outline the utility and applicability of C. elegans as a powerful model organism for mechanistic studies of environmental influences on the epigenome. Our goal in this article is to inform the field of environmental epigenetics of the strengths and limitations of the well-established C. elegans model organism as an emerging model for medium-throughput, in vivo exploration of the role of exogenous chemical stimuli in transcriptional regulation, developmental epigenetic reprogramming, and epigenetic memory and inheritance. As the field of environmental epigenetics matures, and research begins to map mechanisms underlying observed associations, new toolkits and model systems, particularly manipulable, scalable in vivo systems that accurately model human transcriptional regulatory circuits, will provide an essential experimental bridge between in vitro biochemical experiments and mammalian model systems. Environ. Mol. Mutagen. 59:560-575, 2018. © 2018 Wiley Periodicals, Inc.

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Detection of Mitochondrial Toxicity of Environmental Pollutants UsingCaenorhabditis elegans

Cited by 8 publications

References 394 publications

In Vivo Effects of Silver Nanoparticles on Development, Behavior, and Mitochondrial Function are Altered by Genetic Defects in Mitochondrial Dynamics

In Vivo Effects of Silver Nanoparticles on Development, Behavior, and Mitochondrial Function are Altered by Genetic Defects in Mitochondrial Dynamics

Mitochondrial Toxicity

Caenorhabditis elegans as an emerging model system in environmental epigenetics

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