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线粒体电子传递链抑制在肾细胞中的转录谱。

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

机构信息

Division of Molecular and Computational Toxicology, Vrije University Amsterdam, Amsterdam, the Netherlands.

Division of Drug Discovery and Safety, Leiden Academic Centre of Drug Research, Leiden University, Leiden, the Netherlands.

出版信息

Cell Biol Toxicol. 2023 Dec;39(6):3031-3059. doi: 10.1007/s10565-023-09816-7. Epub 2023 Jun 23.

DOI:10.1007/s10565-023-09816-7
PMID:37353587
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10693540/
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.

摘要

分析化学挑战下的转录组变化，通过揭示特定途径的激活和其他转录调控，为化合物的毒性作用模式提供了深入的机制信息。将细胞行为的变化映射到化学刺激上，有助于对化学危害进行特征描述。在这项研究中，我们通过抑制人肾近端小管细胞系（RPTEC/TERT1）中的电子传递链（ETC）来评估线粒体损伤的转录组图谱。我们确定了未折叠蛋白反应途径（UPR），特别是 PERK/ATF4 分支，这是 ETC I、II 和 III 抑制的常见细胞反应。这一发现和具体阐述的基因可能有助于在传统数据和前瞻性转录组研究中识别化学物质的线粒体缺陷。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e7/10693540/ef510ee73514/10565_2023_9816_Fig10_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e7/10693540/bfb6d5a28f7c/10565_2023_9816_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e7/10693540/2a84024624f8/10565_2023_9816_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e7/10693540/696555bb438f/10565_2023_9816_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e7/10693540/ea3eaf576b11/10565_2023_9816_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e7/10693540/93f45ea8ceab/10565_2023_9816_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83e7/10693540/ef510ee73514/10565_2023_9816_Fig10_HTML.jpg

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