FUNDC1-dependent mitophagy induced by tPA protects neurons against cerebral ischemia-reperfusion injury.

Redox Biology
Ying CaiJialing Wu

Abstract

Autophagy of mitochondria, termed mitophagy, plays an important role in cerebral ischemia-reperfusion (IR) injury, but the mechanism is not yet clear. Tissue-type plasminogen activator (tPA) is the most important thrombolytic drug in the clinical treatment of ischemic stroke and has neuroprotective effects. Here, we explored the effects of tPA on neuronal apoptosis and mitophagy following IR. We found that knocking out the tPA gene significantly aggravated brain injury and increased neuronal apoptosis and mitochondrial damage. Exposure of neurons to tPA reduced injury severity and protected mitochondria. Further studies demonstrated that this protective effect of tPA was achieved via regulation of FUNDC1-mediated mitophagy. Furthermore, we found that tPA enhanced the expression level of FUNDC1 by activating the phosphorylation of AMPK. In summary, our results confirm that tPA exerts neuroprotective effects by increasing the phosphorylation of AMPK and the expression of FUNDC1, thereby inhibiting apoptosis and improving mitochondrial function.

References

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Citations

Aug 3, 2021·Frontiers in Aging Neuroscience·Li LeiTao Li
Sep 24, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hong AnXunming Ji

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Methods Mentioned

BETA
PCR
Assay
flow
flow cytometry
confocal microscopy
transfection
confocal

Software Mentioned

Cytoscape

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