Carta, Giada;
van der Stel, Wanda;
Scuric, Emma W. J.;
Capinha, Liliana;
Delp, Johannes;
Bennekou, Susanne Hougaard;
Forsby, Anna;
Walker, Paul;
Leist, Marcel;
van de Water, Bob;
Jennings, Paul
Transcriptional landscape of mitochondrial electron transport chain inhibition in renal cells
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Media type:
E-Article
Title:
Transcriptional landscape of mitochondrial electron transport chain inhibition in renal cells
Contributor:
Carta, Giada;
van der Stel, Wanda;
Scuric, Emma W. J.;
Capinha, Liliana;
Delp, Johannes;
Bennekou, Susanne Hougaard;
Forsby, Anna;
Walker, Paul;
Leist, Marcel;
van de Water, Bob;
Jennings, Paul
imprint:
Springer Science and Business Media LLC, 2023
Description:
<jats:title>Abstract
</jats:title><jats:p>Analysis of the transcriptomic alterations upon chemical challenge, provides in depth mechanistic information on the compound’s toxic mode of action, by revealing specific pathway activation and other transcriptional modulations. Mapping changes in cellular behaviour to chemical insult, facilitates the characterisation of chemical hazard. In this study, we assessed the transcriptional landscape of mitochondrial impairment through the inhibition of the electron transport chain (ETC) in a human renal proximal tubular cell line (RPTEC/TERT1). We identified the unfolded protein response pathway (UPR), particularly the PERK/ATF4 branch as a common cellular response across ETC I, II and III inhibitions. This finding and the specific genes elaborated may aid the identification of mitochondrial liabilities of chemicals in both legacy data and prospective transcriptomic studies.</jats:p>
<jats:p><jats:bold>Graphical abstract</jats:bold></jats:p>