- [CLINICAL AND MOLECULAR HEPATOLOGY] Alcohol-induced oxidative stress triggers mitochondrial Ca²⁺ release through the permeabilit
- 관리자 |
- 2026-04-01 14:55:21|
- 106
- 2026-04-01 14:55:21|
[Title]
[Corresponding Author]
* Won-Il Jeong (wijeong@kaist.ac.kr )
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
2Center for the Hepatic Glutamate and Its Function, KAIST, Daejeon, South Korea.
[Journal]
clinical and molecular hepatology. 2026 Mar 11
https://doi.org/10.3350/cmh.2026.0005
[Abstract]
A chronic-plus-binge ethanol (EtOH) mouse model is employed to investigate the molecular mechanisms of alcohol associated steatohepatitis (ASH). In this model, alcohol-induced reactive oxygen species (ROS) generation and calcium (Ca²⁺) fluctuations in mitochondria drive glutamate release from vesicular glutamate transporter 3 (VGLUT3) granules, activating metabotropic glutamate receptor 5 (mGluR5) in Kupffer cells via pseudosynapse formation between ballooned hepatocytes and Kupffer cells, which leads to hepatocyte death and neutrophil infiltration. However, the underlying mechanism of Ca2+ release from mitochondria post binge is still obscure despite of elevated mitochondrial Ca2+ levels of rat and mouse hepatocytes by chronic alcohol consumption. Additionally, high mitochondrial Ca2+ levels coupled to the ROS production activates mitochondrial permeability transition pore (mPTP) in the mitochondrial membrane, releasing Ca2+ into the cytoplasm. Therefore, we explored whether binge drinking following chronic alcohol exposure exacerbates mitochondrial ROS production and the resultant Ca2+ release through mPTP in ASH models.
Alcohol-induced oxidative stress triggers mitochondrial Ca²⁺ release through the permeability transition pore
[Corresponding Author]
* Won-Il Jeong (wijeong@kaist.ac.kr )
1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
2Center for the Hepatic Glutamate and Its Function, KAIST, Daejeon, South Korea.
[Journal]
clinical and molecular hepatology. 2026 Mar 11
https://doi.org/10.3350/cmh.2026.0005
[Abstract]
A chronic-plus-binge ethanol (EtOH) mouse model is employed to investigate the molecular mechanisms of alcohol associated steatohepatitis (ASH). In this model, alcohol-induced reactive oxygen species (ROS) generation and calcium (Ca²⁺) fluctuations in mitochondria drive glutamate release from vesicular glutamate transporter 3 (VGLUT3) granules, activating metabotropic glutamate receptor 5 (mGluR5) in Kupffer cells via pseudosynapse formation between ballooned hepatocytes and Kupffer cells, which leads to hepatocyte death and neutrophil infiltration. However, the underlying mechanism of Ca2+ release from mitochondria post binge is still obscure despite of elevated mitochondrial Ca2+ levels of rat and mouse hepatocytes by chronic alcohol consumption. Additionally, high mitochondrial Ca2+ levels coupled to the ROS production activates mitochondrial permeability transition pore (mPTP) in the mitochondrial membrane, releasing Ca2+ into the cytoplasm. Therefore, we explored whether binge drinking following chronic alcohol exposure exacerbates mitochondrial ROS production and the resultant Ca2+ release through mPTP in ASH models.
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