TOM7 silencing exacerbates focal cerebral ischemia injury in rat by targeting PINK1/Beclin1-mediated autophagy

• Published in: Behavioural brain research Vol. 360; pp. 113 - 119
• Main Authors: Ning, Jiang, Junyi, Tan, Chang, Meng, Yueting, Wang, Jingyan, Zhang, Jin, Zhu, Jing, Zhao, Yong, Zhao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.03.2019
• Subjects: Autophagy; Cerebral infarction; Photothrombotic stroke model; PINK1; TOM7; Cerebral infarction; Photothrombotic stroke model; TOM7; PINK1; Autophagy
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2018.11.031

•Stroke is a leading cause of death and disability requiring treatments which benefit neuronal survival following cerebral ischemia injury.•Autophagy has been previously shown to attenuate secondary damage after ischemia injury.•We found that the expression of TOM7 was up-regulated after cerebral ischemia injury and peaked at 3 days.•It is the first to demonstrate that TOM7 may exhibit neuro-protective effects by inducing autophagy through the PINK1/Beclin1 pathway. Activated autophagy has been intensively observed in cerebrovascular diseases, including focal cerebral ischemia injury, but its molecular mechanisms remain unclear. TOM7, which is a component of the protein translocase of the outer mitochondrial membrane (TOM) complex, may modulate assembly of the TOM complex. However, an understanding of how TOM7 affects cerebral ischemia injury is limited. In this study, we demonstrate that the expression of TOM7 is up-regulated after a photothrombotic cerebral ischemic model in rats, peaking at 3 days. In addition, TOM7 knockdown may aggravate cerebral ischemic injury and inhibit autophagy after ischemic stroke. Mechanically, TOM7 may regulate autophagy through the PINK1/Beclin1 pathway after cerebral ischemia injury. These results demonstrate that TOM7 silencing may aggravate cerebral ischemia injury through inhibiting PINK1/Beclin1 pathway- mediated autophagy.