简介：人的耳朵是为正常通讯的听觉的一台精细的感觉仪器，并且它的合适的工作高度依赖于mitochondrialoxidativephosphorylation。为nonsyndromic和aminoglycoside-inducedhearing损失的第一mitochondrial点突变在1993被识别。从那以后，很多个继承mitochondrial变化在听见损失被含有。大多数为联系mitochondrialdisorder的听觉损失负责的分子的缺点是在12SrRNA基因和tRNA基因的变化。在这评论，在对正常听觉机制和mitochondrial的短描述以后，我们构画出在联系聋的mitochondrialmutations的鉴定被做了的最近的进展，并且讨论mitochondrial机能障碍怎么贡献听觉损失。

简介：AIM:Todeterminethealterationsinratenterocytemitochondrialrespiratoryfunctionandenzymeactivitiesfollowingtraumaticbraininjury(TBI).METHODS:Fifty-sixmaleSDratswererandomlydividedintosevengroups(8ratsineachgroup):acontrolgroup(ratswithshamoperation)andtraumaticbraininjurygroupsat6,12,24h,days2,3,and7afteroperation.TBImodelswereinducedbyFeendy’sfree-fallingmethod.Mitochondrialrespiratoryfunction(respiratorycontrolratioandADP/Oratio)wasmeasuredwithaClarkoxygenelectrode.TheactivitiesofrespiratorychaincomplexⅠ-Ⅳandrelatedenzymesweredeterminedbyspectrophotometry.RESULTS:Comparedwiththecontrolgroup,themitochondrialrespiratorycontrolratio(RCR)declinedat6handremainedatalowleveluntilday7afterTBI(control,5.42±0.46;6h,5.20±0.18;12h,4.55±0.35;24h,3.75±0.22;2d,4.12±0.53;3d,3.45±0.41;7d,5.23±0.24,P<0.01).Thevalueofphosphate-to-oxygen(P/O)significantlydecreasedat12,24h,day2andday3,respectively(12h,3.30±0.10;24h,2.61±0.21;2d,2.95±0.18;3d,2.76±0.09,P<0.01)comparedwiththecontrolgroup(3.46±0.12).Twotroughsofmitochondrialrespiratoryfunctionwereseenat24handday3afterTBI.TheactivitiesofmitochondrialcomplexⅠ(6h:110±10,12h:115±12,24h:85±9,day2:80±15,day3:65±16,P<0.01)andcomplexⅡ(6h:105±8,12h:110±92,24h:80±10,day2:76±8,day3:68±12,P<0.01)wereincreasedat6hand12hfollowingTBI,andthensignificantlydecreasedat24h,day2andday3,respectively.However,therewerenodifferencesincomplexⅠandⅡactivitiesbetweenthecontrolandTBIgroups.Furthermore,pyruvatedehydrogenase(PDH)activitywassignificantlydecreasedat6handcontinuedupto7dafterTBIcomparedwiththecontrolgroup(6h:90±8,12h:85±10,24h:65±12,day2:60±9,day3:55±6,day7:88±11,P<0.01).Thechangesinα-ketoglutaricdehydrogenase(KGDH)activityweresimilartoPDH,exceptthatthedecreaseinKGDHactivitybeganat12hafterTBI(12h:90±12,24h:80±9,day2:76±15,day3:68±7,

简介：Objective:Tostudytheeffectsofmagnesiumsulfateonbrainmitochondrialrespiratoryfunctioninratsafterexperimentaltraumaticbraininjuryandthepossiblemechanism.Methods:ThemiddledegreebraininjuryinratswasmadebyBIM-IIImulti-functionimpactingmachine.Thebrainmitochondrialrespiratoryfunctionwasmeasuredwithoxygenelectrodeandtheultra-structuralchangeswereobservedwithtransmissionelectronmicroscope(TEM).Results:1.ThebrainmitochondrialrespiratorystageIIIandrespirationcontrolratereducedsignificantlyintheuntreatedgroupswithin24and72hours.ButtreatedGroupAshowedcertaindegreeofrecoveryofrespiratoryfunction;treatedGroupBshowedfurtherimprovement.2.UntreatedGroup,treatedGroupsAandBhaddifferentdegreesofmitochondrialultra-structuraldamagerespectively,whichcouldbeattenuatedafterthetreatmentwithmagnesiumsulfate.Conclusions:Themitochondrialrespiratoryfunctiondecreasessignificantlyaftertraumaticbraininjury.ButitcanbeapparentlyimprovedaftermagnesiumsulfatemanagementalongwiththeattenuateddamageofmitochondriadiscoveredbyTEM.Thelongercourseoftreatmentcanobtainabetterimprovementofmitochondrialrespiratoryfunction.

简介：ObjectiveToestablishananimalmodelofsuddenonsetsensorineuralhearingloss(SSNHL)tostudyitsmechanisms.MaterialsandmethodsTheinnerearwasexposedto3-nitropropionicacidat0.5mol/L(3-NP(H))and0.3mol/L(3-NP(L))throughtheroundwindowmembranefor30minutesin50maleguineapigs.Thresholdsofauditorybrainstemresponses(ABR)wereestablishedbeforethetreatmentandretestedat4hours,1day,3daysand6daysfollowing3-NPexposure.Controlanimalsweretreatedwithphosphatebufferedsaline(PBS)andtheirABRswereretestedat4hoursand1dayafterthetreatment.Animalsweremonitoredfornystagmusandposturalsignsofvestibulardysfunction,usingadigitalvideocamera,followingthetreatmentprocedure.Specimensweretakenat12hours,1day,3daysand7daysfollowing3-NP(H)exposureandembeddedinJB4forlightmicroscopyobservation.ResultsABRswerelostinallanimalstestedat4hoursfollowing3-NP(H)exposure.TherateofcompleteABRlossdecreasedaspost-treatmenttesttimeincreased.ABRswerelostin80%(4/5)oftheanimalsat1dayafterexposureto3-NP(L).Spontaneoushorizontalnystagmuswithafastphaseawayfromthetreatedeardevelopedinall3-NP(H)-treatedanimalsandin20%(1/5)oftheanimalsexposedto3-NP(L),exceptfortheonetreatedbilaterally.Variousdegreeofposturaldisturbancesconsistentwithunilateralvestibulardysfunction,suchasspontaneousbarrelrollingtowardstheexposuresidewhilewalking,wereseeninallanimalsexposedto3-NP(H)and40%(2/5)ofanimalsexposedto3-NP(L),exceptfortheoneanimaltreatedbilaterally,whichshowednosignsofimbalance.Bothnystagmusandposturaldisturbancesresolvedin2daysfollowing3-NPexposure.HistologicalstudyshowedtemporaryedematintheorganorCorti,Claudiuscellsandtheinnersulcuscells3daysafter3-NP(H)treatment.Enlargementofintercellularspaceinthespiralprominencewasfirstnoticedat12hourspost-3-NP(H)exposure,progressedatd

简介：在源于mitochondrial机能障碍的氧化phosphorylation的改变长被假设了涉及tumorigenesis。线粒体最近被显示了在调整规划房间死亡和房间增长起一个重要作用。而且，mitochondrialDNA(mtDNA)变化在各种各样的癌症房间被发现了。然而，在tumorigenesis的这些mtDNA变化的角色仍然保持大部分未知。这评论集中于基本mitochondrial遗传，mtDNA变化和与癌症联系的结果的mitochondrial机能障碍。潜在的分子的机制，调停从mtDNA变化的致病和到tumorigenesis的mitochondrial机能障碍也被讨论。

简介：Basedonthefirstlawofthermodynamicsandthethermaldiffusionequation,thededucedtheoreticalmodelofmitochondrialthermogenesissatisfiestheLaplaceequationandisaspecialcaseofthethermaldiffusionequation.Themodelsettlesthelong-standingquestionoftheabilitytoincreasecellulartemperaturebyendogenousthermogenesisandexplainsthethermogeniccharacteristicsofbrownadipocytes.Themodelandcalculationsalsosuggestthatthenumberoffreeavailableprotonsisthemajorlimitingfactorforendogenousthermogenesisanditsspeed.

简介：MitochondrialtRNAmutationsareoneoftheimportantcausesofbothsyndromicandnon-syndromicdeafness.Ofthose,syndromicdeafness-associatedtRNAmutationssuchastRNALeu(UUR)3243A>Gareoftenpresentinheteroplasmy,whilenon-syndromicdeafness-associatedtRNAmutationsincludingtRNASer(UCN)7445A>Gareofteninhomplasmyorinhighlevelsofheteroplasmy.ThesetRNAmutationsaretheprimarymutationsleadingtohearingloss.However,othertRNAmutationssuchastRNAThr15927G>AandtRNASer(UCN)7444G>AmayactinsynergywiththeprimarymitochondrialDNAmutations,modulatingthephenotypicmanifestationoftheprimarymitochondrialDNAmutations.ThesestRNAmutationscausestructuralandfunctionalalteration.AfailureintRNAmetabolismcausedbythesetRNAmutationsimpairedmitochondrialtranslationandrespiration,therebycausingmitochondrialdysfunctionsresponsiblefordeafness.Thesedataoffervaluableinformationfortheearlydiagnosis,managementandtreatmentofmaternallyinheriteddeafness.

简介：Themitochondrial12SrRNAhasbeenshowntobethehotspotformutationsassociatedwithbothaminoglycoside-inducedandnon-syndromichearingloss.Ofallthemutations,thehomoplasmicA1555GandC1494Tmutationsatahighlyconserveddecodingregioninthe12SrRNAhavebeenassociatedwithaminoglycoside-inducedandnon-syndromichearinglossinmanyfamiliesworldwide.TheA1555GorC1494Tmutationisexpectedtoformnovel1494C-G1555or1494U-A1555base-pairatthehighlyconservedA-siteof12SrRNA.ThesetransitionsmakethesecondarystructureofthisRNAmorecloselyresemblethecorrespondingregionofbacterial16SrRNA.Thus,thenewU-AorG-Cpairin12SrRNAcreatedbytheC1494TorA1555Gtransitionfacilitatesthebindingofaminoglycosides,therebyaccountingforthefactthattheexposuretoaminoglycosidescaninduceorworsenhearinglossinindividualscarryingthesemutations.Furthermore,thegrowthdefectandimpairmentofmitochondrialtranslationwereobservedincelllinescarryingtheA1555GorC1494Tmutationinthepresenceofhighconcentrationofaminoglycosides.Inaddition,nuclearmodifiergenesandmitochondrialhaplotypesmodulatethephenotypicmanifestationoftheA1555GandC1494Tmutations.TheseobservationsprovidethedirectgeneticandbiochemicalevidencesthattheA1555GorC1494TmutationisapathogenicmtDNAmutationassociatedwithaminoglycoside-inducedandnonsyndromichearingloss.Therefore,thesedatahavebeenprovidingvaluableinformationandtechnologytopredictwhichindividualsareatriskforototoxicity,toimprovethesafetyofaminoglycosideantibiotictherapy,andeventuallytodecreasetheincidenceofdeafness.

简介：Stressinducedtheseriousdisorderofcardiacfunctionandcardiovasculardiseases.Apoptosisisthecellularbasisinstressinducedcardiacinjury.Inourpreviousstudywefoundthatmanystressorsresultedinmitochondrialdamage.Itiscertainthatmitochondriaisimportantmediatorintriggeringapoptoticcelldeath,butthemechanism,bywhichthestressinducedmitochondrialinjuryleadstocardiomyocyteapoptosis,remainsunclear.Wedesignedthepresentstudytoinvestigatethechangesofthemitochondriaincardiomyocytesundergoingstressanditsroleininducingapoptosis.Herewereportedthatstresschangedthemembranefluidityofmitochondriaandinducedthelipidperoxidationofmitochondrialmembranein

简介：Introduction,Theroleofleftventriculographyhasevolvedradicallyoverthelasthalf-century,buthasreceivedlittlenoticeintheacademicliterature.ThetechniqueandfrequencyofuseofleftventriculographyvaryacrossregionsoftheUnitedStates,institutions,andindividuals.

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简介：Thereisaccumulatingevidencethatcysteinesulfenation（cys-SOH）inproteinsplaysanimportantroleincellularresponsetooxidativestress.Thepurposeofthepresentstudywastoidentifymitochondrialproteinsthatundergochangesincys-SOHduringaging.Studieswereconductedinratswhentheywere5or30monthsofage.FollowingblockingoffreeproteinthiolswithN-ethylmaleimide,proteinsulfenicacidswerereducedbyarsenitetofreethiolgroupsthatweresubsequentlylabeledwithbiotin-maleimide.Sampleswerethencomparativelyanalyzedbytwo-dimensionalWesternblots,andproteinsshowingchangesinsulfenationwereselectivelyidentifiedbymassspectrometrypeptidesequencing.Asaresult,fiveproteinswereidentified.Proteinsshowinganage-relateddecreaseinsulfenationincludepyruvatecarboxylaseandpyruvatedehydrogenase;whilethoseshowinganage-relatedincreaseinsulfenationincludeaconitase,mitofilin,andtubulin（α-1）.Resultsofthepresentstudyprovideageneralpictureofmitochondrialproteinsulfenationinbrainoxidativestressandimplicatetheinvolvementofproteinsulfenationinoveralldeclineofmitochondrialfunctionduringbrainaging.

简介：MutationsinmitochondrialtRNAgeneshavebeenshowntobeassociatedwithmaternallyinheritedsyn-dromicandnon-syndromicdeafness.Amongthose,mutationssuchastRNALeu(UUR)3243A>Gassociatedwithsyndromicdeafnessareoftenpresentinheteroplasmy,andthenon-syndromicdeafness-associatedtRNAmu-tationsincludingtRNASer(UCN)7445A>Gareofteninhomoplasmyorinhighlevelsofheteroplasmy.ThesetRNAmutationsaretheprimaryfactorsunderlyingthedevelopmentofhearingloss.However,othertRNAmutationssuchastRNAThr15927G>AandtRNASer(UCN)7444G>Aareinsufficienttoproduceadeafnessphe-notype,butalwaysactinsynergywiththeprimarymitochondrialDNAmutations,andcanmodulatetheirphenotypicmanifestation.ThesetRNAmutationsmayalterthestructureandfunctionofthecorrespondingmitochondrialtRNAsandcausefailuresintRNAsmetabolism.Thereby,theimpairmentofmitochondrialproteinsynthesisandsubsequentdefectsinrespirationcausedbythesetRNAmutations,resultsinmitochon-drialdysfunctionsandeventuallyleadstothedevelopmentofhearingloss.Here,wesummarizedthedeaf-ness-associatedmitochondrialtRNAmutationsanddiscussedthepathophysiologyofthesemitochondrialtRNAmutations,andwehopethesedatawillprovideafoundationfortheearlydiagnosis,management,andtreatmentofmaternallyinheriteddeafness.

简介：ToinvestigategeneticmechanismsofhighaltitudeadaptationsofnativemammalsontheTibetanPlateau,wecomparedmitochondrialsequencesoftheendangeredPantholopshodgsoniiwithitslowlanddistantrelativesOvisariesandCaprahircus,aswellasothermammals.ThecompletemitochondrialgenomeofP.hodgsonii(16,498bp)revealedasimilargeneorderasofothermammals.Becauseoftandemduplications,thecontrolregionofP.hodgsoniimitochondrialgenomeisshorterthanthoseofO.ariesandC.hircus,butlongerthanthoseofBosspecies.PhylogeneticanalysisbasedonalignmentsoftheentirecytochromebgenessuggestedthatP.hodgsoniiismorecloselyrelatedtoO.ariesandC.hircus,ratherthantospeciesoftheAntilopinaesubfamily.TheestimateddivergencetimebetweenP.hodgsoniiandO.ariesisabout2.25millionyearsago.FurtheranalysisonnaturalselectionindicatedthattheCOXI(cytochromecoxidasesubunitI)genewasunderpositiveselectioninP.hodgsoniiandBosgrunniens.Consideringthesameclimatesandenvironmentssharedbythesetwomammalianspecies,weproposedthatthemitochondrialCOXIgeneisprobablyrelevantforthesenativemammalstoadaptthehighaltitudeenvironmentuniquetotheTibetanPlateau.

简介：Aminoglycosides(AmAn)arewidelyusedfortheirgreatefficiencyagainstgram-negativebacterialinfections.However,theycanalsoinduceototoxichearingloss,whichhasaffectedmillionsofpeoplearoundtheworld.Aspreviouslyreported,individualsbearingmitochondrialDNAmutationsinthe12SrRNAgene,suchasm.1555A>Gandm.1494C>T,aremorepronetoAmAn-inducedototoxicity.Thesemutationscausehumanmitochondrialribosomestomorecloselyresemblebacterialribosomesandenableastrongeraminoglycosideinteraction.Consequently,exposuretoAmAncaninduceorworsenhearinglossintheseindividuals.Furthermore,awiderangeofseverityandpenetranceofhearinglosswasobservedamongfamiliescarryingthesemutations.StudieshaverevealedthatthesemitochondriamutationsaretheprimarymolecularmechanismofgeneticsusceptibilitytoAmAnototoxicity,thoughnuclearmodifiergenesandmitochondrialhaplotypesareknowntomodulatethephenotypicmanifestation.

简介：MtDNAwassuccessfullyextractedfromtenindividualbones(femurs)inthetombsofancientJushiinTurfanbasin,datedbacktotheyearabout3000-2500yearsago.Bymeansoffouroverlappingprimers,wegotnucleotidesequenceofthe218bplength.AncientmtDNAwasanalyzedbythesequencingofhypervariableregionⅠofthemtDNAcontrolregion.Theresultshowsthat9haplotypeswith24polymorphicsiteswereobtained.ThephylogeneticanalysisindicatedthatMongoliansandAltaiarethepopulationgeneticallyclosesttotheJushigroupsandJushimtDNApoolbeinganadmixtureofeasternAsianandEuropeanlineages.SoourpreliminarydataimplythatanancientminglingofEuro-AsianpopulationhadexistedinTurfanbasinpriortotheearlyIronAge.

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简介：AbstractBackground:Previous studies have reported that mitochondrial dysfunction participates in the pathological process of osteoarthritis (OA). However, studies that improve mitochondrial function are rare in OA. Mitochondrial transfer from mesenchymal stem cells (MSCs) to OA chondrocytes might be a cell-based therapy for the improvement of mitochondrial function to prevent cartilage degeneration. This study aimed to determine whether MSCs can donate mitochondria and protect the mitochondrial function and therefore reduce cartilage degeneration.Methods:Bone-marrow-derived mesenchymal stromal cells (BM-MSCs) were harvested from the marrow cavities of femurs and tibia in young rats. OA chondrocytes were gathered from the femoral and tibial plateau in old OA model rats. BM-MSCs and OA chondrocytes were co-cultured and mitochondrial transfer from BM-MSCs to chondrocytes was identified. Chondrocytes with mitochondria transferred from BM-MSCs were selected by fluorescence-activated cell sorting. Mitochondrial function of these cells, including mitochondrial membrane potential (Δψm), the activity of mitochondrial respiratory chain (MRC) enzymes, and adenosine triphosphate (ATP) content were quantified and compared to OA chondrocytes without mitochondrial transfer. Chondrocytes proliferation, apoptosis, and secretion ability were also analyzed between the two groups.Results:Mitochondrial transfer was found from BM-MSCs to OA chondrocytes. Chondrocytes with mitochondrial from MSCs (MSCs + OA group) showed increased mitochondrial membrane potential compared with OA chondrocytes without mitochondria transfer (OA group) (1.79 ± 0.19 vs. 0.71 ± 0.12, t = 10.42, P < 0.0001). The activity of MRC enzymes, including MRC complex I, II, III, and citrate synthase was also improved (P < 0.05). The content of ATP in MSCs + OA group was significantly higher than that in OA group (161.90 ± 13.49 vs. 87.62 ± 11.07 nmol/mg, t = 8.515, P < 0.0001). Meanwhile, we observed decreased cell apoptosis (7.09% ± 0.68% vs.15.89% ± 1.30%, t = 13.39, P < 0.0001) and increased relative secretion of type II collagen (2.01 ± 0.14 vs.1.06 ± 0.11, t = 9.141, P = 0.0008) and proteoglycan protein (2.08 ± 0.20 vs. 0.97 ± 0.12, t = 8.227, P = 0.0012) in MSCs + OA group, contrasted with OA group.Conclusions:Mitochondrial transfer from BM-MSCs provided protection for OA chondrocytes against mitochondrial dysfunction and degeneration through improving mitochondrial function, cell proliferation, and inhibiting apoptosis in chondrocytes. This finding may offer a new therapeutic direction for OA.

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简介：ULTRAFunctionEnterpriseCompanyLimited(UFECL)isaSino-foreignjointventurewhichpro-ducesthecompoundsofREwithhighpurityinChina.Itpossessesadvancedinternationalseparationtechnol-ogyofrareearthandanalytical-testinginstrument.