Transcriptional landscape of mitochondrial electron transport chain inhibition in renal cells-Reference-Cited by-同舟云学术

Transcriptional landscape of mitochondrial electron transport chain inhibition in renal cells

Published:2023-06-23 Issue:6 Volume:39 Page:3031-3059
ISSN:0742-2091
Container-title:Cell Biology and Toxicology
language:en
Short-container-title:Cell Biol Toxicol

Author:

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

Abstract

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

Funder

EU-ToxRisk project funded by the European Union's Horizon 2020

Publisher

Springer Science and Business Media LLC

Subject

Health, Toxicology and Mutagenesis,Cell Biology,Toxicology

Link

https://link.springer.com/content/pdf/10.1007/s10565-023-09816-7.pdf

Reference71 articles.

1. Adams CJ, et al. Structure and molecular mechanism of ER stress signaling by the unfolded protein response signal activator IRE1. Front Mol Biosci. 2019; 6(MAR). https://doi.org/10.3389/FMOLB.2019.00011.

2. Anders S, Huber W. Differential expression analysis for sequence count data. Genome Biol Biomed Central. 2010;11(10):R106. https://doi.org/10.1186/gb-2010-11-10-r106.

3. Aschauer L, et al. Delineation of the key aspects in the regulation of epithelial monolayer formation. Mol Cell Biol. 2013;33(13):2535–50. https://doi.org/10.1128/mcb.01435-12.

4. Barrientos A, Moraes CT. Titrating the effects of mitochondrial complex I impairment in the cell physiology. J Biol Chem. 1999;274(23):16188–97. https://doi.org/10.1074/jbc.274.23.16188. (Â© 1999 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology).

5. Bell SM. et al. An integrated chemical environment to support 21st-century toxicology. Environ Health Perspect. 2017; 125(5). https://doi.org/10.1289/EHP1759.

Cited by 2 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. The UPR^ERgoverns the cell-specific response of human dopaminergic neurons to mitochondrial stress;2024-06-17

2. Definition of the Neurotoxicity-Associated Metabolic Signature Triggered by Berberine and Other Respiratory Chain Inhibitors;Antioxidants;2023-12-28