Perfluorodecanoic acid (PFDA) increases oxidative stress through inhibition of mitochondrial β-oxidation

Raimund Widhalm; Sebastian Granitzer; Benjamin Natha; Ottavia Zoboli; Julia Derx; Harald Zeisler; Hans Salzer; Stefan Weiss; Nicole Schmitner; Robin A Kimmel; Tamina Österreicher; Raimund Oberle; Markus Hengstschläger; Martin Distel; Claudia Gundacker

doi:10.1016/j.envpol.2024.125595

Perfluorodecanoic acid (PFDA) increases oxidative stress through inhibition of mitochondrial β-oxidation

Raimund Widhalm, Sebastian Granitzer, Benjamin Natha, Ottavia Zoboli, Julia Derx, Harald Zeisler, Hans Salzer, Stefan Weiss, Nicole Schmitner, Robin A Kimmel, Tamina Österreicher, Raimund Oberle, Markus Hengstschläger, Martin Distel, Claudia Gundacker

Division of Paediatrics and Adolescent Medicine (University Hospital Tulln)

Research output: Journal article (peer-reviewed) › Journal article

1 Citation (Scopus)

Abstract

PER: and polyfluoroalkyl substances (PFAS) are a large group of synthetic organic chemicals that are ubiquitous environmental pollutants. Among PFAS, perfluorodecanoic acid (PFDA) is one of the most toxic compounds, but the molecular basis behind its toxicity is not fully understood. In an interspecies comparison with placental cells (HTR-8/SVneo) and zebrafish embryos, we demonstrate that PFDA induces mitochondrial dysfunction and impairs fatty acid β-oxidation. Reduced β-oxidation leads to less TCA cycle activity, resulting in less NADH and consequently NADPH production. Thereby NADPH-dependent glutathione recycling is impaired, increasing cellular oxidative stress that can only be partially compensated by NRF2 activation.

Original language	English
Article number	125595
Pages (from-to)	125595
Journal	Environmental Pollution
Volume	367
DOIs	https://doi.org/10.1016/j.envpol.2024.125595
Publication status	E-pub ahead of print - 27 Dec 2024

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Widhalm, R., Granitzer, S., Natha, B., Zoboli, O., Derx, J., Zeisler, H., Salzer, H., Weiss, S., Schmitner, N., Kimmel, R. A., Österreicher, T., Oberle, R., Hengstschläger, M., Distel, M., & Gundacker, C. (2024). Perfluorodecanoic acid (PFDA) increases oxidative stress through inhibition of mitochondrial β-oxidation. Environmental Pollution, 367, 125595. Article 125595. Advance online publication. https://doi.org/10.1016/j.envpol.2024.125595

@article{26253637838d4728b0ade525e48bd29d,

title = "Perfluorodecanoic acid (PFDA) increases oxidative stress through inhibition of mitochondrial β-oxidation",

abstract = "PER: and polyfluoroalkyl substances (PFAS) are a large group of synthetic organic chemicals that are ubiquitous environmental pollutants. Among PFAS, perfluorodecanoic acid (PFDA) is one of the most toxic compounds, but the molecular basis behind its toxicity is not fully understood. In an interspecies comparison with placental cells (HTR-8/SVneo) and zebrafish embryos, we demonstrate that PFDA induces mitochondrial dysfunction and impairs fatty acid β-oxidation. Reduced β-oxidation leads to less TCA cycle activity, resulting in less NADH and consequently NADPH production. Thereby NADPH-dependent glutathione recycling is impaired, increasing cellular oxidative stress that can only be partially compensated by NRF2 activation.",

author = "Raimund Widhalm and Sebastian Granitzer and Benjamin Natha and Ottavia Zoboli and Julia Derx and Harald Zeisler and Hans Salzer and Stefan Weiss and Nicole Schmitner and Kimmel, {Robin A} and Tamina {\"O}sterreicher and Raimund Oberle and Markus Hengstschl{\"a}ger and Martin Distel and Claudia Gundacker",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = dec,

day = "27",

doi = "10.1016/j.envpol.2024.125595",

language = "English",

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Widhalm, R , Granitzer, S, Natha, B, Zoboli, O, Derx, J, Zeisler, H, Salzer, H, Weiss, S, Schmitner, N, Kimmel, RA, Österreicher, T, Oberle, R, Hengstschläger, M, Distel, M & Gundacker, C 2024, 'Perfluorodecanoic acid (PFDA) increases oxidative stress through inhibition of mitochondrial β-oxidation', Environmental Pollution, vol. 367, 125595, pp. 125595. https://doi.org/10.1016/j.envpol.2024.125595

TY - JOUR

T1 - Perfluorodecanoic acid (PFDA) increases oxidative stress through inhibition of mitochondrial β-oxidation

AU - Widhalm, Raimund

AU - Granitzer, Sebastian

AU - Natha, Benjamin

AU - Zoboli, Ottavia

AU - Derx, Julia

AU - Zeisler, Harald

AU - Salzer, Hans

AU - Weiss, Stefan

AU - Schmitner, Nicole

AU - Kimmel, Robin A

AU - Österreicher, Tamina

AU - Oberle, Raimund

AU - Hengstschläger, Markus

AU - Distel, Martin

AU - Gundacker, Claudia

PY - 2024/12/27

Y1 - 2024/12/27

N2 - PER: and polyfluoroalkyl substances (PFAS) are a large group of synthetic organic chemicals that are ubiquitous environmental pollutants. Among PFAS, perfluorodecanoic acid (PFDA) is one of the most toxic compounds, but the molecular basis behind its toxicity is not fully understood. In an interspecies comparison with placental cells (HTR-8/SVneo) and zebrafish embryos, we demonstrate that PFDA induces mitochondrial dysfunction and impairs fatty acid β-oxidation. Reduced β-oxidation leads to less TCA cycle activity, resulting in less NADH and consequently NADPH production. Thereby NADPH-dependent glutathione recycling is impaired, increasing cellular oxidative stress that can only be partially compensated by NRF2 activation.

AB - PER: and polyfluoroalkyl substances (PFAS) are a large group of synthetic organic chemicals that are ubiquitous environmental pollutants. Among PFAS, perfluorodecanoic acid (PFDA) is one of the most toxic compounds, but the molecular basis behind its toxicity is not fully understood. In an interspecies comparison with placental cells (HTR-8/SVneo) and zebrafish embryos, we demonstrate that PFDA induces mitochondrial dysfunction and impairs fatty acid β-oxidation. Reduced β-oxidation leads to less TCA cycle activity, resulting in less NADH and consequently NADPH production. Thereby NADPH-dependent glutathione recycling is impaired, increasing cellular oxidative stress that can only be partially compensated by NRF2 activation.

UR - http://www.scopus.com/inward/record.url?scp=85215077085&partnerID=8YFLogxK

U2 - 10.1016/j.envpol.2024.125595

DO - 10.1016/j.envpol.2024.125595

M3 - Journal article

C2 - 39734044

SN - 0269-7491

VL - 367

SP - 125595

JO - Environmental Pollution

JF - Environmental Pollution

M1 - 125595

ER -

Perfluorodecanoic acid (PFDA) increases oxidative stress through inhibition of mitochondrial β-oxidation

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