8mitochondria disease(1).pptVIP免费

MitochondrialMedicineBinLu,Ph.D.MITOCHONDRIAThemitochondrionGeneralInformation线粒体（mitochondrion，复数mitochondria）•细胞进行生物氧化和能量转换的场所•sometimesdescribedas"cellularpowerplants”,becausetheirprimaryfunctionistoconvertorganicmaterialsintoenergyintheformofATPStructureofMitochondrionMitochondriahave:anoutermembranethatenclosestheentirestructureaninnermembranethatenclosesafluid-filledmatrixbetweenthetwoistheintermembranespacetheinnermembraneiselaboratelyfoldedwithshelflikecristaeprojectingintothematrix.Structure7Cristae:Foldsofinnermembrane,extendingintothmatrix.Theyincreasethesurfaceareaofinnermembraneandraisetheworkingefficiencyofmitochondria.*Cristae*Cristae什么是线粒体疾病？Whatismitochondrialdisease?•线粒体功能异常为主要病因的一大类疾病；主要是由于以下基因突变引起。mtDNA编码线粒体蛋白的nDNAmtDNA和编码线粒体蛋白的DNA线粒体的主要功能体现在氧化磷酸化系统：产生能量，生成氧线粒体的主要功能体现在氧化磷酸化系统：产生能量，生成氧自由基，调节程序化细胞死亡自由基，调节程序化细胞死亡,,即细胞凋亡即细胞凋亡((apoptosis)apoptosis)。。20%areduetomtDNAmutations;80%nuclearmutationsMitochondrialdisordersDefinitionClinicallyheterogeneousdisordersthatareduetomitochondrialrespiratorychaindysfunction(Wallace1999),causedbymutationsinthemtDNAORnDNAthatencodesforanyofthefollows:1.structuralproteinoftheOXPHOScomplexes2.proteinrequiredforassemblyofOXPHOScomplexes3.proteinsinvolvedinmtDNAtranslation4.proteinsinvolvedinmtDNAmaintenance5.ProteinsinvolvedinmitochondrialfussionandfissionHistoryofMitochondrialDiseases:1962Luftdescribesfirstcaseofaeuthyroidwomanwithextremehypermetabolismandgiganticmitochondriainmuscle1962MiltonShydescribesmitochondrialproliferationinmyopathicpatients1962W.KingEngelapplieshistochemicaltechniquestomuscle,usesmodifiedGomoritrichromestain1975L.P.Rowlandlumper/splitterdebateregardingKSS/progressiveophthalmoplegia1975KoenigsbergerdescribeacaseofMELAS1981mtDNAgenomemapped1982RowlandandFukuharapresentindependentpapersregard...