N6-methyladenosine demethylase FTO impairs hepatic ischemia-reperfusion injury via inhibiting Drp1-mediated mitochondrial fragmentation.
Cell Death Dis
; 12(5): 442, 2021 05 04.
Article
em En
| MEDLINE
| ID: mdl-33947842
ABSTRACT
Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role and the underlying regulatory mechanism in the liver remain largely unexplored. In the present study, we showed that fat mass and obesity-associated protein (FTO, an m6A demethylase) was involved in mitochondrial function during hepatic ischemia-reperfusion injury (HIRI). We found that the expression of m6A demethylase FTO was decreased during HIRI. In contrast, the level of m6A methylated RNA was enhanced. Adeno-associated virus-mediated liver-specific overexpression of FTO (AAV8-TBG-FTO) ameliorated the HIRI, repressed the elevated level of m6A methylated RNA, and alleviated liver oxidative stress and mitochondrial fragmentation in vivo and in vitro. Moreover, dynamin-related protein 1 (Drp1) was a downstream target of FTO in the progression of HIRI. FTO contributed to the hepatic protective effect via demethylating the mRNA of Drp1 and impairing the Drp1-mediated mitochondrial fragmentation. Collectively, our findings demonstrated the functional importance of FTO-dependent hepatic m6A methylation during HIRI and provided valuable insights into the therapeutic mechanisms of FTO.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Mitocôndrias Hepáticas
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Traumatismo por Reperfusão
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Adenosina
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Dinaminas
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Dioxigenase FTO Dependente de alfa-Cetoglutarato
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Fígado
Limite:
Animals
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China