MCU inhibition protects against intestinal ischemiaâreperfusion by inhibiting Drp1-dependent mitochondrial fission.
Free Radic Biol Med
; 221: 111-124, 2024 Aug 20.
Article
em En
| MEDLINE
| ID: mdl-38763207
ABSTRACT
Intestinal ischemiaâreperfusion (IIR) injury is a common complication of surgery, but clear molecular insights and valuable therapeutic targets are lacking. Mitochondrial calcium overload is an early sign of various diseases and is considered a vital factor in ischemiaâreperfusion injury. The mitochondrial calcium uniporter (MCU), which is located on the inner mitochondrial membrane, is the primary mediator of calcium ion entry into the mitochondria. However, the specific mechanism of MCU in IIR injury remains to be clarified. In this study, we generated an IIR model using C57BL/6 mice and Caco-2 cells and found increases in the calcium levels and MCU expression following IIR injury. The specific inhibition of MCU markedly attenuated IIR injury. Moreover, MCU knockdown alleviates mitochondrial dysfunction by reducing oxidative stress and apoptosis. Mechanistically, MCU knockdown substantially reduced the translocation of Drp1 and thus its binding to Fis1 receptors, resulting in decreased mitochondrial fission. Taken together, our findings demonstrated that MCU is a novel upstream regulator of Drp1 in ischemiaâreperfusion and represents a predictive and therapeutic target for IIR.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Cálcio
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Traumatismo por Reperfusão
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Apoptose
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Dinaminas
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Dinâmica Mitocondrial
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Camundongos Endogâmicos C57BL
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Mitocôndrias
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article