Perfluorodecanoic acid (PFDA) increases oxidative stress through inhibition of mitochondrial β-oxidation
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.
Authors
- Sebastian Granitzer (ORCID: https://orcid.org/0000-0003-0963-5275)
- Robin A. Kimmel (ORCID: https://orcid.org/0000-0002-9283-1252)
- Martin Distel (ORCID: https://orcid.org/0000-0001-5942-0817)
- Julia Derx (ORCID: https://orcid.org/0000-0002-9931-088X)
- Markus Hengstschläger (ORCID: https://orcid.org/0000-0002-3342-7583)
- Harald Zeisler (ORCID: https://orcid.org/0000-0003-4995-4561)
- Claudia Gundacker (ORCID: https://orcid.org/0000-0003-4093-3780)
- Raimund Widhalm (ORCID: https://orcid.org/0000-0002-8257-9903)
- Tamina Österreicher
- Ottavia Zoboli (ORCID: https://orcid.org/0000-0002-2128-5434)
- Raimund Oberle (ORCID: https://orcid.org/0000-0001-6701-4130)
- Hans Salzer
- Stefan Weiß (ORCID: https://orcid.org/0009-0001-3077-0386)
- Nicole Schmitner (ORCID: https://orcid.org/0009-0009-3036-866X)
- Benjamin Natha
Institutions
- TU Wien (AT)
- Universität Innsbruck (AT)
- Environment Agency Austria (AT)
- Universitätsklinikum Tulln (AT)
- Institute for Environmental Management (US)
- Cancer Research Institute of the Slovak Academy of Sciences (SK)
- St Anna Children's Hospital (AT)
- Interuniversity Cooperation Centre Water & Health (AT)
- Medical University of Vienna (AT)
Publication Details
- Journal
- Environmental Pollution
- Published
- 2024-12-27
- DOI
- https://doi.org/10.1016/j.envpol.2024.125595
- Citations
- 15
- Primary Topic
- Per- and polyfluoroalkyl substances research
- Type
- article
- Field-Weighted Citation Impact
- 3.76
Funders
- Gesellschaft für Forschungsförderung Niederösterreich
- Vienna Science and Technology Fund
- Austrian Science Fund
- Österreichische Forschungsförderungsgesellschaft