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

Environ Pollut. 2024 Dec 27:125595. doi: 10.1016/j.envpol.2024.125595. Online ahead of print.

Authors

Affiliations

¹ Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria; Exposome Austria, Research Infrastructure and National EIRENE Hub, Austria. Electronic address: [email protected].
² Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria; Exposome Austria, Research Infrastructure and National EIRENE Hub, Austria.
³ Zebrafish Platform Austria for Preclinical Drug Screening (ZANDR), St. Anna Children's Cancer Research Institute, Vienna, Austria.
⁴ Institute for Water Quality and Resource Management, TU Wien, Vienna.
⁵ Institute of Hydraulic Engineering and Water Resources Management, TU Wien, Vienna, Austria; Interuniversity Cooperation Centre Water and Health, Vienna, Austria.
⁶ Department of Obstetrics and Gynecology, Medical University Vienna, Austria.
⁷ Clinic for Pediatrics and Adolescent Medicine, University Clinic Tulln, Tulln, Austria.
⁸ Environment Agency Austria, Vienna, Austria.
⁹ Institute of Molecular Biology, Center for Molecular Biosciences Innsbruck (CMBI), Leopold Franzens University Innsbruck, Innsbruck, Austria.
¹⁰ Center for Pathobiochemistry and Genetics, Institute of Medical Chemistry and Pathobiochemistry, Medical University of Vienna, Vienna, Austria.
¹¹ Center for Pathobiochemistry and Genetics, Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria.
¹² Zebrafish Platform Austria for Preclinical Drug Screening (ZANDR), St. Anna Children's Cancer Research Institute, Vienna, Austria; Innovative Cancer Models, St. Anna Children's Cancer Research Institute, Vienna, Austria; Division of Pediatric Hematology and Oncology, Intermountain Primary Children's Hospital, Huntsman Cancer Institute, Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, USA.

PMID: 39734044
DOI: 10.1016/j.envpol.2024.125595

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.

Keywords: Toxicity; glutathione; placenta; zebrafish.