粒体自噬
SIRT3
IDH2型
帕金
衰老
细胞生物学
品脱1
线粒体
生物
锡尔图因
下调和上调
活性氧
线粒体ROS
自噬
乙酰化
细胞凋亡
内科学
生物化学
突变
IDH1
医学
基因
疾病
帕金森病
作者
Ikjun Lee,Shuyu Piao,Seonhee Kim,Harsha Nagar,Si Hwan Choi,Min-Soo Kim,Giang-Huong Vu,Byeong Hwa Jeon,Cuk-Seong Kim
出处
期刊:Antioxidants
[MDPI AG]
日期:2023-02-27
卷期号:12 (3): 585-585
被引量:1
标识
DOI:10.3390/antiox12030585
摘要
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.
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