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Updated: Jul 29, 2025
Two-vessel Occlusion Mouse Model of Cerebral Ischemia-reperfusion
Published on: March 1, 2019
Immp2l Mutation Induces Mitochondrial Membrane Depolarization and Complex III Activity Suppression after Middle
Yi Ma1,2, Rui-Min Liang3, Ning Ma3
1Department of Pathology, School of Basic Medicine, Ningxia Medical University, Yinchuan, 750004, China. mayi_nxmu@163.com.
Objective:
We previously reported that mutations in inner mitochondrial membrane peptidase 2-like (Immp2l) increase infarct volume, enhance superoxide production, and suppress mitochondrial respiration after transient cerebral focal ischemia and reperfusion injury. The present study investigated the impact of heterozygous Immp2l mutation on mitochondria function after ischemia and reperfusion injury in mice.
Methods:
Mice were subjected to middle cerebral artery occlusion for 1 h followed by 0, 1, 5, and 24 h of reperfusion. The effects of Immp2l+/- on mitochondrial membrane potential, mitochondrial respiratory complex III activity, caspase-3, and apoptosis-inducing factor (AIF) translocation were examined.
Results:
Immp2l+/- increased ischemic brain damage and the number of TUNEL-positive cells compared with wild-type mice. Immp2l+/- led to mitochondrial damage, mitochondrial membrane potential depolarization, mitochondrial respiratory complex III activity suppression, caspase-3 activation, and AIF nuclear translocation.
Conclusion:
The adverse impact of Immp2l+/- on the brain after ischemia and reperfusion might be related to mitochondrial damage that involves depolarization of the mitochondrial membrane potential, inhibition of the mitochondrial respiratory complex III, and activation of mitochondria-mediated cell death pathways. These results suggest that patients with stroke carrying Immp2l+/- might have worse and more severe infarcts, followed by a worse prognosis than those without Immp2l mutations.
Insights
Heterozygous Immp2l mutations worsen brain damage after stroke by impairing mitochondrial function and activating cell death pathways. This suggests a poorer prognosis for stroke patients with Immp2l mutations.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Ischemic Stroke Research
Background:
- Inner mitochondrial membrane peptidase 2-like (Immp2l) mutations are linked to increased infarct volume and impaired mitochondrial function post-stroke.
- Previous studies indicated Immp2l mutations exacerbate cerebral ischemia-reperfusion injury.
Purpose of the Study:
- To investigate the impact of heterozygous Immp2l mutation (Immp2l+/-) on mitochondrial function following transient cerebral focal ischemia and reperfusion injury in mice.
Main Methods:
- Mice underwent middle cerebral artery occlusion (1h) followed by reperfusion (0-24h).
- Assessed mitochondrial membrane potential, mitochondrial respiratory complex III activity, caspase-3 activation, and apoptosis-inducing factor (AIF) translocation.
Main Results:
- Immp2l+/- mice exhibited increased ischemic brain damage and TUNEL-positive cells compared to wild-type.
- Mitochondrial damage, including membrane potential depolarization and suppressed complex III activity, was observed.
- Caspase-3 activation and AIF nuclear translocation were also noted in Immp2l+/- mice.
Conclusions:
- Immp2l+/- exacerbates brain injury post-stroke via mitochondrial dysfunction and apoptosis.
- Mitochondrial damage, complex III inhibition, and activation of cell death pathways contribute to stroke severity.
- Immp2l+/- may indicate a worse prognosis and more severe infarcts in stroke patients.
