Immp2l Mutation Induces Mitochondrial Membrane Depolarization and Complex Ⅲ Activity Suppression after Middle Cerebral Artery Occlusion in Mice
作者机构：Department of PathologySchool of Basic MedicineNingxia Medical UniversityYinchuan 750004China Department of Ningxia Key Laboratory of Cerebrocranial DiseasesNingxia Medical UniversityYinchuan 750004China Department of PathologyXi'an No.3 Hospitalthe Affiliated Hospital of Northwest UniversityXi'an 710018China Department of AnesthesiologyNingxia Chinese Medicine Research CenterYinchuan 750004China Institute for Regenerative MedicineWake Forest University School of MedicineWinston-Salem 27110USA Department of Pharmaceutical SciencesBiomanufacturing Research Institute and Technological Enterprise(BRITE)North Carolina Central UniversityDurham 27707USA
出 版 物：《当代医学科学(英文)》 (Current Medical Science)
年 卷 期：2023年第43卷第3期
页 面：478-488页
核心收录：
学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学]
基 金：This study was supported by the National Natural Science Foundation of China(Nos.81360196,81760240 the Natural Science Foundation of Ningxia(No.2022AAC03159) the Ningxia Innovation Team of the Foundation and Clinical Research of Diabetes and Its Complications(No.NXKJT2019010).
主 题：cerebral ischemia inner mitochondrial membrane peptidase 2-like mitochondrial membrane potential mitochondrial complex III apoptosis
摘 要：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.
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