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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'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.

SUBMITTER: Carta G 

PROVIDER: S-EPMC10693540 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Transcriptional landscape of mitochondrial electron transport chain inhibition in renal cells.

Carta Giada G   van der Stel Wanda W   Scuric Emma W J EWJ   Capinha Liliana L   Delp Johannes J   Bennekou Susanne Hougaard SH   Forsby Anna A   Walker Paul P   Leist Marcel M   van de Water Bob B   Jennings Paul P  

Cell biology and toxicology 20230623 6

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 re  ...[more]

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