Transcriptional landscape of mitochondrial electron transport chain inhibition in renal cells

Giada Carta; Wanda van der Stel; Emma W.J. Scuric; Liliana Capinha; Johannes Delp; Susanne Hougaard Bennekou; Anna Forsby; Paul Walker; Marcel Leist; Bob van de Water; Paul Jennings

doi:10.1007/s10565-023-09816-7

Transcriptional landscape of mitochondrial electron transport chain inhibition in renal cells

Giada Carta^*
, Wanda van der Stel
, Emma W.J. Scuric
, Liliana Capinha
, Johannes Delp
, Susanne Hougaard Bennekou
, Anna Forsby
, Paul Walker
, Marcel Leist
, Bob van de Water
, Paul Jennings

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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. Graphical abstract: [Figure not available: see fulltext.].

Original language	English
Pages (from-to)	3031-3059
Number of pages	29
Journal	Cell biology and toxicology
Volume	39
Issue number	6
Early online date	23 Jun 2023
DOIs	https://doi.org/10.1007/s10565-023-09816-7
Publication status	Published - Dec 2023

Bibliographical note

Funding Information:
This work was funded by the EU-ToxRisk project, grant agreement No 681002, funded by the European Union's Horizon 2020 research and innovation programme.

Publisher Copyright:
© 2023, The Author(s).

Funding

This work was funded by the EU-ToxRisk project, grant agreement No 681002, funded by the European Union's Horizon 2020 research and innovation programme.

Funders	Funder number
Horizon 2020
Horizon 2020 Framework Programme	681002

Keywords

In vitro
Mitochondria
Renal
Stress pathway
Transcriptomic

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10.1007/s10565-023-09816-7

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title = "Transcriptional landscape of mitochondrial electron transport chain inhibition in renal cells",

abstract = "Analysis of the transcriptomic alterations upon chemical challenge, provides in depth mechanistic information on the compound{\textquoteright}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. Graphical abstract: [Figure not available: see fulltext.].",

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note = "Funding Information: This work was funded by the EU-ToxRisk project, grant agreement No 681002, funded by the European Union's Horizon 2020 research and innovation programme. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

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doi = "10.1007/s10565-023-09816-7",

language = "English",

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AU - Carta, Giada

AU - van der Stel, Wanda

AU - Scuric, Emma W.J.

AU - Capinha, Liliana

AU - Delp, Johannes

AU - Bennekou, Susanne Hougaard

AU - Forsby, Anna

AU - Walker, Paul

AU - Leist, Marcel

AU - van de Water, Bob

AU - Jennings, Paul

N1 - Funding Information: This work was funded by the EU-ToxRisk project, grant agreement No 681002, funded by the European Union's Horizon 2020 research and innovation programme. Publisher Copyright: © 2023, The Author(s).

PY - 2023/12

Y1 - 2023/12

N2 - 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. Graphical abstract: [Figure not available: see fulltext.].

AB - 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. Graphical abstract: [Figure not available: see fulltext.].

KW - In vitro

KW - Mitochondria

KW - Renal

KW - Stress pathway

KW - Transcriptomic

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JO - Cell biology and toxicology

JF - Cell biology and toxicology

IS - 6

ER -

Transcriptional landscape of mitochondrial electron transport chain inhibition in renal cells

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Keywords

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