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West Ashley Library
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Folly Beach Library
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Edgar Allan Poe/Sullivan's Island Library
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Wando Mount Pleasant Library
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Village Library
9 a.m. - 1 p.m.
Phone: (843) 884-9741
St. Paul's/Hollywood Library
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McClellanville Library
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MCU Upregulation Overactivates Mitophagy by Promoting VDAC1 Dimerization and Ubiquitination in the Hepatotoxicity of Cadmium.
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- Author(s): Liu, Cong1,2; Li, Hui-Juan3; Duan, Wei-Xia1,2; Duan, Yu1,2; Yu, Qin1,2; Zhang, Tian1,4; Sun, Ya-Pei1; Li, Yuan-Yuan1,2; Liu, Yong-Sheng1,2; Xu, Shang-Cheng1,2
- Source:
Advanced Science. 3/3/2023, Vol. 10 Issue 7, p1-17. 17p.- Subject Terms:
- Source:
- Additional Information
- Abstract: Cadmium (Cd) is a high-risk pathogenic toxin for hepatic diseases. Excessive mitophagy is a hallmark in Cd-induced hepatotoxicity. However, the underlying mechanism remains obscure. Mitochondrial calcium uniporter (MCU) is a key regulator for mitochondrial and cellular homeostasis. Here, Cd exposure upregulated MCU expression and increased mitochondrial Ca2+ uptake are found. MCU inhibition through siRNA or by Ru360 significantly attenuates Cd-induced excessive mitophagy, thereby rescues mitochondrial dysfunction and increases hepatocyte viability. Heterozygous MCU knockout mice exhibit improved liver function, ameliorated pathological damage, less mitochondrial fragmentation, and mitophagy after Cd exposure. Mechanistically, Cd upregulates MCU expression through phosphorylation activation of cAMP-response element binding protein at Ser133(CREBS133) and subsequent binding of MCU promoter at the TGAGGTCT, ACGTCA, and CTCCGTGATGTA regions, leading to increased MCU gene transcription. The upregulated MCU intensively interacts with voltage-dependent anion-selective channel protein 1 (VDAC1), enhances its dimerization and ubiquitination, resulting in excessive mitophagy. This study reveals a novel mechanism, through which Cd upregulates MCU to enhance mitophagy and hepatotoxicity. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Advanced Science is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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