Elaidic acid leads to mitochondrial dysfunction via mitochondria-associated membranes triggers disruption of mitochondrial calcium fluxes
Elaidic acid (EA) stimulation can lead to endoplasmic reticulum stress (ERS), accompanied by a large release of Ca2+, and ultimately the activation of NLRP3 inflammasome in Kupffer cells (KCs). Mitochondrial instability or dysfunction may be the key stimulating factors to activate NLRP3 inflammasome...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Tsinghua University Press
2024-01-01
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| Series: | Food Science and Human Wellness |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213453023001349 |
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| Summary: | Elaidic acid (EA) stimulation can lead to endoplasmic reticulum stress (ERS), accompanied by a large release of Ca2+, and ultimately the activation of NLRP3 inflammasome in Kupffer cells (KCs). Mitochondrial instability or dysfunction may be the key stimulating factors to activate NLRP3 inflammasome, and sustained Ca2+ transfer can result in mitochondrial dysfunction. We focused on KCs to explore the damage to mitochondria by EA. After EA stimulation, cells produced an oxidative stress (OS) response with a significant increase in ROS release. Immunoprecipitation experiments and the addition of inhibitors revealed that the increase in the level of intracellular Ca2+ led to Ca2+ accumulation in the mitochondrial matrix via mitochondria-associated membranes (MAMs). This was accompanied by a significant release of mROS, loss of MMP and ATP, and a significant increase in mitochondrial permeability transition pore opening, ultimately leading to mitochondrial instability. These findings confirmed the mechanism that EA induced mitochondrial Ca2+ imbalance in KCs via MAM, ultimately leading to mitochondrial dysfunction. Meanwhile, EA induced OS and the decrease of MMP and ATP in rat liver, and significant lesions were found in liver mitochondria. Swelling of the inner mitochondrial cristae and mitochondrial vacuolization occurred, with a marked increase in lipid droplets. |
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| ISSN: | 2213-4530 |