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
N1 - Publisher Copyright:
© 2024 The Authors
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 -