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IDH2 Deficiency Promotes Endothelial Senescence by Eliciting miR-34b/c-Mediated Suppression of Mitophagy and Increased ROS Production
- Source :
- Antioxidants, Vol 12, Iss 3, p 585 (2023)
- Publication Year :
- 2023
- Publisher :
- MDPI AG, 2023.
-
Abstract
- Endothelial senescence impairs vascular function and thus is a primary event of age-related vasculature diseases. Isocitrate dehydrogenase 2 (IDH2) plays an important role in inducing alpha-ketoglutarate (α-KG) production and preserving mitochondrial function. However, the mechanism and regulation of IDH2 in endothelial senescence have not been elucidated. We demonstrated that downregulation of IDH2 induced accumulation of miR-34b/c, which impaired mitophagy and elevated mitochondrial reactive oxygen species (ROS) levels by inhibiting mitophagy-related markers (PTEN-induced putative kinase 1 (PINK1), Parkin, LC-II/LC3-I, and p62) and attenuating Sirtuin deacetylation 3 (Sirt3) expression. The mitochondrial dysfunction induced by IDH2 deficiency disrupted cell homeostasis and the cell cycle and led to endothelial senescence. However, miR-34b/c inhibition or α-KG supplementation restored Sirt3, PINK1, Parkin, LC-II/LC3-I, p62, and mitochondrial ROS levels, subsequently alleviating endothelial senescence. We showed that IDH2 played a crucial role in regulating endothelial senescence via induction of miR-34b/c in endothelial cells.
Details
- Language :
- English
- ISSN :
- 20763921
- Volume :
- 12
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- Antioxidants
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.2c14f9a0e4f93aec57faf67430351
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/antiox12030585