
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 447
Title
Kidney failure induced by inhibition of mitochondrial electron transfer chain through apoptosis, inflammation and oxidative stress pathways
Short name
Graphical Representation
Point of Contact
Contributors
- Yann GUEGUEN
- Marie FREREJACQUES
- Brendan Ferreri-Hanberry
Status
Author status | OECD status | OECD project | SAAOP status |
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Under development: Not open for comment. Do not cite |
This AOP was last modified on May 08, 2022 11:33
Revision dates for related pages
Page | Revision Date/Time |
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Inhibition, Mitochondrial Electron Transport Chain Complexes | March 01, 2022 10:45 |
Increase, Mitochondrial Dysfunction | February 09, 2022 11:48 |
Decrease, Mitochondrial membrane potential | April 30, 2020 12:41 |
Altered gene expression, NRF2 dependent antioxidant pathway | August 19, 2021 07:35 |
Inhibition, Nuclear factor kappa B (NF-kB) | May 03, 2021 02:57 |
Activation of ER stress | November 02, 2020 07:09 |
Increased, Oxidative Stress | February 03, 2022 14:20 |
Increase, Apoptosis | April 15, 2017 16:17 |
Increase in inflammation | May 03, 2019 14:27 |
Occurrence, renal proximal tubular necrosis | September 16, 2017 10:16 |
Occurrence, Kidney toxicity | March 04, 2022 10:58 |
Increased, Kidney Failure | January 16, 2019 08:57 |
Inhibition, ECT complexes of the respiratory chain leads to Decrease, MMP | April 08, 2022 08:27 |
Decrease, MMP leads to Increase, Mt Dysfunction | April 08, 2022 08:28 |
Increase, Mt Dysfunction leads to Altered expression of NRF2 pathway-dependent genes | April 08, 2022 08:29 |
Increase, Mt Dysfunction leads to Inhibition, Nuclear factor kappa B (NF-kB) | April 08, 2022 08:30 |
Increase, Mt Dysfunction leads to Increase, Apoptosis | April 08, 2022 08:31 |
Altered expression of NRF2 pathway-dependent genes leads to ER stress | April 08, 2022 08:31 |
Altered expression of NRF2 pathway-dependent genes leads to Increased, Oxidative Stress | April 08, 2022 08:32 |
ER stress leads to Increase, Apoptosis | April 08, 2022 08:32 |
Inhibition, Nuclear factor kappa B (NF-kB) leads to Increase in inflammation | April 08, 2022 08:32 |
Increased, Oxidative Stress leads to Occurrence, renal proximal tubular necrosis | December 03, 2016 16:38 |
Increase, Apoptosis leads to Occurrence, renal proximal tubular necrosis | April 08, 2022 08:34 |
Increase in inflammation leads to Occurrence, renal proximal tubular necrosis | April 08, 2022 08:34 |
Occurrence, renal proximal tubular necrosis leads to Occurrence, Kidney toxicity | April 08, 2022 08:35 |
Occurrence, Kidney toxicity leads to Increased, Kidney Failure | April 08, 2022 08:35 |
Uranium | August 05, 2021 14:28 |
Uranium, soluble salts | April 08, 2022 08:55 |
Abstract
U metal-ions are filtered through the glomerular membrane of the kidneys, then concentrate in cortical and juxtaglomerular areas and bind to the brush border membrane of the proximal convoluted tubules. U uptake by epithelial cells occurs through endocytosis and the sodium-dependent phosphate co-transporter (NaPi-IIa). Molecular key events start with U induce mitochondrial ETC inhibition (KE1), decrease MMP (KE2) and mitochondrial disruption (KE3). The collapse of mitochondrial membrane potential triggers the Nrf2 (KE3), NF-κB (KE4) or endoplasmic reticulum-stress (KE5) pathways. The resulting cellular key events include oxidative stress (KE6), apoptosis (KE7), and pro-inflammatory effects (KE8). Finally, the main adverse outcome is tubular cell necrosis (KE9), leading to kidney toxicity (KE10) and then kidney failure (AO).
Background (optional)
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Sequence | Type | Event ID | Title | Short name |
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1 | KE | 105 | Inhibition, Mitochondrial Electron Transport Chain Complexes | Inhibition, ECT complexes of the respiratory chain |
2 | KE | 1770 | Decrease, Mitochondrial membrane potential | Decrease, MMP |
3 | KE | 1968 | Increase, Mitochondrial Dysfunction | Increase, Mt Dysfunction |
4 | KE | 1917 | Altered gene expression, NRF2 dependent antioxidant pathway | Altered expression of NRF2 pathway-dependent genes |
5 | KE | 202 | Inhibition, Nuclear factor kappa B (NF-kB) | Inhibition, Nuclear factor kappa B (NF-kB) |
6 | KE | 1815 | Activation of ER stress | ER stress |
7 | KE | 1088 | Increased, Oxidative Stress | Increased, Oxidative Stress |
8 | KE | 1365 | Increase, Apoptosis | Increase, Apoptosis |
9 | KE | 1633 | Increase in inflammation | Increase in inflammation |
10 | KE | 1097 | Occurrence, renal proximal tubular necrosis | Occurrence, renal proximal tubular necrosis |
11 | KE | 814 | Occurrence, Kidney toxicity | Occurrence, Kidney toxicity |
12 | AO | 759 | Increased, Kidney Failure | Increased, Kidney Failure |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
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Network View
Stressors
Name | Evidence Term |
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Uranium | |
Uranium, soluble salts |