title: Deficiency in the inner mitochondrial membrane peptidase 2-like (Immp21) gene increases ischemic brain damage and impairs mitochondrial function.
abstract: Mitochondrial dysfunction plays an important role in mediating ischemic brain damage. Immp2l is an inner mitochondrial membrane peptidase that processes mitochondrial protein cytochrome c1 (Cyc1). Homozygous mutation of Immp2l (Immp2l(Tg(Tyr)979Ove) or Immp2l(-/-)) elevates mitochondrial membrane potential, increases superoxide (O(2)(-)) production in the brain and impairs fertility. The objectives of this study are to explore the effects of heterozygous mutation of Immp2l (Immp2l(+/-)) on ischemic outcome and to determine the influence of Immp2l deficiency on brain mitochondria after stroke. Male Immp2l(+/-) and wild-type (WT) mice were subjected to 1-h focal cerebral ischemia. Their brains were harvested after 5 and 24-h of reperfusion. The results showed that infarct volume and DNA oxidative damage significantly increased in the Immp2l(+/-) mice. There were no obvious cerebral vasculature abnormalities between the two types of mice viewed by Indian ink perfusion. The increased damage in Immp2l(+/-) mice was associated with early increase in O(2)(-) production. Mitochondrial respiratory rate, total mitochondrial respiratory capacity and mitochondrial respiratory complex activities were decreased at 5-h of recirculation in Immp2l(+/-) mice compared to WT mice. Our results suggest that Immp2l deficiency increases ischemic brain damage by enhancing O(2)(-) production and damaging mitochondrial functional performance.
authors.affiliation: Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, NC 27707, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ma
authors.forename: Suresh L
authors.initials: SL
authors.lastname: Mehta
authors.forename: Baisong
authors.initials: B
authors.lastname: Lu
authors.forename: P Andy
authors.initials: PA
authors.lastname: Li
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000473:pathology / Q000648:ultrastructure*; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D002545:Brain Ischemia / Q000150:complications; D002941:Circle of Willis / Q000473:pathology; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D003997:Dicarbethoxydihydrocollidine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000172:deficiency*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000473:pathology* / Q000502:physiology; D024101:Mitochondrial Proteins / Q000172:deficiency*; D010101:Oxygen Consumption / Q000187:drug effects / Q000235:genetics; D013997:Time Factors
chemical_list: D024101:Mitochondrial Proteins; C514241:dihydroethidine; D003997:Dicarbethoxydihydrocollidine; D010450:Endopeptidases; C568497:inner mitochondrial membrane peptidase 2-like protein, mouse