Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways

被引：93

作者：

Duan Chenyang ^{[1
]}

Kuang Lei ^{[1
]}

Xiang Xinming ^{[1
]}

Zhang Jie ^{[1
]}

Zhu Yu ^{[1
]}

Wu Yue ^{[1
]}

Yan Qingguang ^{[1
]}

Liu Liangming ^{[1
]}

Li Tao ^{[1
]}

机构：

[1] Army Med Univ, Daping Hosp, State Key Lab Trauma Burns & Combined Injury, Dept Res Inst Surg 2, Chongqing 400042, Peoples R China

来源：

CELL DEATH & DISEASE | 2020年 / 11卷 / 04期

基金：

中国国家自然科学基金;

关键词：

ACTIVATED PROTEIN-KINASE; FOCAL CEREBRAL-ISCHEMIA; CELL-DEATH; VASCULAR HYPOREACTIVITY; HYPOXIA-ISCHEMIA; AUTOPHAGY ACTIVATION; HEMORRHAGIC-SHOCK; NEURONAL INJURY; PROTECTIVE ROLE; REPERFUSION;

D O I：

10.1038/s41419-020-2461-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The adaptation of mitochondrial homeostasis to ischemic injury is not fully understood. Here, we studied the role of dynamin-related protein 1 (Drp1) in this process. We found that mitochondrial morphology was altered in the early stage of ischemic injury while mitochondrial dysfunction occurred in the late stage of ischemia. Drp1 appeared to inhibit mitophagy by upregulating mito-Clec16a, which suppressed mito-Parkin recruitment and subsequently impaired the formation of autophagosomes in vascular tissues after ischemic injury. Moreover, ischemia-induced Drp1 activation enhanced apoptosis through inducing mitochondrial translocation of BAX and thereby increasing release of Cytochrome C to activate caspase-3/-9 signalling. Furthermore, Drp1 mediated metabolic disorders and inhibited the levels of mitochondrial glutathione to impair free radical scavenging, leading to further increases in ROS and the exacerbation of mitochondrial dysfunction after ischemic injury. Together, our data suggest a critical role for Drp1 in ischemic injury.

引用

页数：19

共 62 条

[61]

Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance [J].