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1、ClinicalScience(2014)127,367373(PrintedinGreatBritain)doi:10.1042/CS20140101TheBioenergeticHealthIndex:anewconceptinmitochondrialtranslationalresearchBaluK.CHACKO∗,PhilipA.KRAMER∗,SaranyaRAVI∗,GloriaA.BENAVIDES∗,TaneciaMITCHELL∗,BrianP.DRANKA,DavidFERRICK,Ashw
2、aniK.SINGAL§,ScottW.BALLINGER∗,ShannonM.BAILEY,RobertW.HARDY∗,JianhuaZHANG∗,DeguiZHI¶andVictorM.DARLEY-USMAR∗1∗MitochondrialMedicineLaboratory,UniversityofAlabamaatBirmingham,Birmingham,AL35294,U.S.A.DepartmentofPathology,UniversityofAlabamaatBirmingham,Birmi
3、ngham,AL35294,U.S.A.SeahorseBioscience,NorthBillerica,MA01862,U.S.A.§DivisionofGastroenterologyandHepatology,DepartmentofInternalMedicine,UniversityofAlabamaatBirmingham,Birmingham,AL35294,U.S.A.DepartmentofVeteranAffairsMedicalCenter,Birmingham,AL35294,U.S.A
4、.¶DepartmentofBiostatistics,UniversityofAlabamaatBirmingham,Birmingham,AL35294,U.S.A.AbstractBioenergeticshasbecomecentraltoourunderstandingofpathologicalmechanisms,thedevelopmentofnewtherapeuticstrategiesandasabiomarkerfordiseaseprogressioninneurodegeneration
5、,diabetes,cancerandcardiovasculardisease.Akeyconceptisthatthemitochondrioncanactasthecanaryinthecoalminebyservingasanearlywarningofbioenergeticcrisisinpatientpopulations.Weproposethatnewclinicalteststomonitorchangesinbioenergeticsinpatientpopulationsareneededt
6、otakeadvantageoftheearlyandsensitiveabilityofbioenergeticstodetermineseverityandprogressionincomplexandmultifactorialdiseases.Withtherecentdevelopmentofhigh-throughputassaystomeasurecellularenergeticfunctioninthesmallnumberofcellsthatcanbeisolatedfromhumanbloo
7、dtheseclinicaltestsarenowfeasible.Wehaveshownthatthesequentialadditionofwell-characterizedinhibitorsofoxidativephosphorylationallowsabioenergeticprofiletobemeasuredincellsisolatedfromnormalorpathologicalsamples.FromthesedataweproposethatasinglevaluetheBioenerge
8、ticHealthIndex(BHI)canbecalculatedtorepresentthepatientscompositemitochondrialprofileforaselectedcelltype.InthepresentHypothesispaper,wediscusshowBHIcouldserveasadynamicindexofbioen
