Caenorhabditis elegans chronically exposed to a Mn/Zn ethylene-bis-dithiocarbamate fungicide show mitochondrial Complex I inhibition and increased reactive oxygen species

Bailey, Denise C.; Todt, Callie E.; Orfield, Sarah E.; Denney, Rachel D.; Snapp, Isaac B.; Negga, Rekek; Montgomery, Kara M.; Bailey, Andy; Pressley, Aireal S.; Traynor, Wendy L.; Fitsanakis, Vanessa A.

doi:10.1016/j.neuro.2016.07.011

Cited by 25 publications

(19 citation statements)

References 52 publications

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“…Studying whole nematodes, Fitsanakis and colleagues showed that Mn ++ exposure led to defective mitochondrial complex I function, with an increase in hydrogen peroxide concentrations (Bailey et al 2016;Todt et al 2016). In response to the increase in hydrogen peroxide, the expression of a glutathione S-transferase reporter (Pgst-4::gfp) was also increased in the exposed animals.…”

Section: Toxicologymentioning

confidence: 99%

Cell Biology of the Mitochondrion

2017

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In the article by A. M. van der Bliek, M. M. Sedensky, and P. G. Morgan entitled "Cell Biology of the Mitochondrion" on page 855, the second full paragraph incorrectly attributed the development of a luciferase-expressing strain in Caenorhabditis elegans to the Meyer laboratory. The sentence beginning "Perhaps most importantly. . ." was deleted and replaced with the following sentences:"In the Glover and Pettitt laboratories, Lagido et al. (2008) developed a luciferase-expressing strain that allowed in vivo assessment of relative ATP levels in C. elegans. They later described the use of this strain for monitoring toxicant effects on mitochondrial function (McLaggan et al. 2012; Lagido et al. 2015). Members from the Meyer laboratory extended the use of this strain to allow rapid evaluation of the effects of toxicants on mitochondrial function, particularly the electron transport chain, glycolysis, and fatty acid oxidation (Luz et al. 2016b)."The following references were added to the Literature Cited section:

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Section: Toxicologymentioning

confidence: 99%

Cell Biology of the Mitochondrion

2017

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“…Protocols for synchronization, treatment, and endpoint assays used in our lab were previously published in detail (Bailey et al , 2016; Todt et al , 2016). Briefly, C. elegans were grown at 20°C on 8P plates (51.3 mM NaCl, 25.0 g bactoagar/L, 20.0 g bactopeptone/L, 1 mM CaCl 2 , 500 µM KH 2 PO 4 (pH 6), 13 µM cholesterol (95% ethanol), and 1 mM MgSO 4 ) with a lawn of NA22 E. coli (grown in 16 g tryptone/L, 10 g yeast extract/L, 85.5 mM NaCl) until gravid.…”

Section: 0 Materials and Methodsmentioning

confidence: 99%

Chronic exposure to a glyphosate-containing pesticide leads to mitochondrial dysfunction and increased reactive oxygen species production in Caenorhabditis elegans

Bailey

Todt

Burchfield

et al. 2018

Environmental Toxicology and Pharmacology

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Glyphosate-containing herbicides are among the most widely-used in the world. Although glyphosate itself is relatively non-toxic, growing evidence suggests that commercial herbicide formulations may lead to increased oxidative stress and mitochondrial inhibition. In order to assess these mechanisms in vivo, we chronically (24h) exposed Caenorhabditis elegans to various concentrations of the glyphosate-containing herbicide TouchDown (TD). Following TD exposure, we evaluated the function of specific mitochondrial electron transport chain complexes. Initial oxygen consumption studies demonstrated inhibition in mid- and high-TD concentration treatment groups compared to controls. Results from tetramethylrhodamine ethyl ester and ATP assays indicated reductions in the proton gradient and ATP levels, respectively. Additional studies were designed to determine whether TD exposure resulted in increased reactive oxygen species (ROS) production. Data from hydrogen peroxide, but not superoxide or hydroxyl radical, assays showed statistically significant increases in this specific ROS. Taken together, these data indicate that exposure of Caenorhabditis elegans to TD leads to mitochondrial inhibition and hydrogen peroxide production.

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“…Relative steady-state ATP levels were determined as previously described (Bailey et al 2016). First, 200 L4, 50 8-day old, or 50 12-day old nematodes were loaded into a white 96-well plate (3 wells per strain per treatment) in 50μl k-medium, and then 50μl of Promega Mitochondrial ToxGlo assay medium (Promega, Madison, WI) was added to each well.…”

Section: Methodsmentioning

confidence: 99%

Deficiencies in mitochondrial dynamics sensitize Caenorhabditis elegans to arsenite and other mitochondrial toxicants by reducing mitochondrial adaptability

et al. 2017

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Mitochondrial fission, fusion, and mitophagy are interlinked processes that regulate mitochondrial shape, number, and size, as well as metabolic activity and stress response. The fundamental importance of these processes is evident in the fact that mutations in fission (DRP1), fusion (MFN2, OPA1), and mitophagy (PINK1, PARK2) genes can cause human disease (collectively >1/10,000). Interestingly, however, the age of onset and severity of clinical manifestations varies greatly between patients with these diseases (even those harboring identical mutations), suggesting a role for environmental factors in the development and progression of certain mitochondrial diseases. Using the model organism Caenorhabditis elegans, we screened ten mitochondrial toxicants (2, 4-dinitrophenol, acetaldehyde, acrolein, aflatoxin B1, arsenite, cadmium, cisplatin, doxycycline, paraquat, rotenone) for increased or decreased toxicity in fusion (fzo-1, eat-3)-, fission (drp-1)-, and mitophagy (pdr-1, pink-1)-deficient nematodes using a larval growth assay. In general, fusion-deficient nematodes were the most sensitive to toxicants, including aflatoxin B1, arsenite, cisplatin, paraquat, and rotenone. Because arsenite was particularly potent in fission- and fusion-deficient nematodes, and hundreds of millions of people are chronically exposed to arsenic, we investigated the effects of these genetic deficiencies on arsenic toxicity in more depth. We found that deficiencies in fission and fusion sensitized nematodes to arsenite-induced lethality throughout aging. Furthermore, low-dose arsenite, which acted in a “mitohormetic” fashion by increasing mitochondrial function (in particular, basal and maximal oxygen consumption) in wild-type nematodes by a wide range of measures, exacerbated mitochondrial dysfunction in fusion-deficient nematodes. Analysis of multiple mechanistic changes suggested that disruption of pyruvate metabolism and Krebs cycle activity underlie the observed arsenite-induced mitochondrial deficits, and these disruptions are exacerbated in the absence of mitochondrial fusion. This research demonstrates the importance of mitochondrial dynamics in limiting arsenite toxicity by permitting mitochondrial adaptability. It also suggests that individuals suffering from deficiencies in mitodynamic processes may be more susceptible to the mitochondrial toxicity of arsenic and other toxicants.

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Caenorhabditis elegans chronically exposed to a Mn/Zn ethylene-bis-dithiocarbamate fungicide show mitochondrial Complex I inhibition and increased reactive oxygen species

Cited by 25 publications

References 52 publications

Cell Biology of the Mitochondrion

Cell Biology of the Mitochondrion

Chronic exposure to a glyphosate-containing pesticide leads to mitochondrial dysfunction and increased reactive oxygen species production in Caenorhabditis elegans

Deficiencies in mitochondrial dynamics sensitize Caenorhabditis elegans to arsenite and other mitochondrial toxicants by reducing mitochondrial adaptability

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