Salicylate-induced loose coupling: protonmotive force measurements

TY - JOUR

T1 - Salicylate-induced loose coupling

T2 - protonmotive force measurements

AU - Haas, Richard

AU - Davies Parker, W.

AU - Stumpf, David

AU - Eguren, Luigi A.

N1 - Funding Information: Salicylated oess timulateo ligomycins ensitiveA TPasesi n in rat liver mitochondritah rougha n increasein state4 somep reparation\[s5 \]b, ut this is not the explanatiofno r proton conductance\[ 13\].W ith both salicylate and the state4 acceleratiown ith salicylatein rat liver. Our octanoatein creaseds, ubstratec onsumptionw ill result protonmotivef orce measurementssh owed a small along with the acceleratedo xygen consumptiono f a reduction in protonmotivefo rce and transmembrane" looselyc oupled"s tate4 . Both octanoataen d salicylate electricapl otentiailn state3 which was not statistically have effectso n mitochondriaolx idativep hosphorylation significanTt.h isp rotonmotivfoer cew ass ufficientto sustain whichm ayi nduceo r potentiatteh em itochondridala mage phosphorylatioonf ADP to ATP. However, in state 4 occurringin Reye Syndrome. small changesin protonmotivfeo rceand transmembrane In summary,r ecente vidences uggeststh at salicylate electricapl otentiawl erea ssociatewd ith a 2-fold increase ingestionis associatewd ith Reye SyndromeW. e studied in oxygenc onsumptiorna tea nda 4-foldi ncreasien proton the effecto f salicylateo n isolatedr at liver mitochondria, conductanceT.h is suggeststh at in state 4 an increased confirminpgr eviouws orks howinga nu ncouplinegf fecta nd numbero f protonc hannelas re availableI.t follows that investigatintgh e mechanismof this action by use of a increasedo xygen and substratec onsumptionw ill be protonmotivfeo rce assay. Salicylate( 1 mM) produced required to maintain the protonmotivefo rce. These loosec ouplingo f state4 rateso f oxidativep hosphorylation measuremenptrso vided irecte videnceth atthe actiono f allowing preservation of ATP production. The salicylatoe n mitochondraiat this concentratioisn t hato f a protonmotivefo rce and the transmembraneele ctrical protoni onophore. potentiawl erer educedin state4 . Salicylatea ppearedto The increased ADP/O ratios observed in this be acting as a proton ionophorea s shown by a 4-fold polarographsict udyw ith 1 mM salicylatem ayr esultf rom increasein state4 protonc onductance. the 3-min preincubationin which matrix adenine nucleotidesm ay be lost or translocasien hibitionm ay Acknowledgements--Twhoirsk w ass upportebdy a Clinical becomea significanfta ctor. ResearcGh rantf romt heM uscularD ystrophAy ssociation; The inhibitiono f state3 rateso f oxygenc onsumption NIH Program Project Grant HD08315, Center Grant (Table 1) which reacheds ignificancfeo r ol-ketoglutarateH D04024, and National Research Service Award has beeno bservedb efore\ [4,8 \].P ossiblee xplanationasr e HD07096, all from NICHD; Pediatrica nd Adult CRC an inhibitiono f ~-ketoglutaradteeh ydrogenawseh ichw as Grant RR00069 from the General Clinical Research first noted by Kaplan et al. \[12\]o r, alternativelya,n Center'sP rogramo f the Divisiono f ResearchR esources; inhibitorye ffecto n the ATP-ADP translocas\e[9 \]. fundingf rom the Friedreich'As taxiaGroup in America, Octanoatme aya lsob eof significancien the pathogenesis Inc.; and an AcademicS enatere searcshu pporgt rantf rom of Reye'ss yndromaen di nducesa similar" loosec oupling" the Universityo f California,S anDiego.

PY - 1985/3/15

Y1 - 1985/3/15

UR - http://www.scopus.com/inward/record.url?scp=0021952904&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021952904&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(85)90774-9

DO - 10.1016/0006-2952(85)90774-9

M3 - Article

C2 - 3977963

AN - SCOPUS:0021952904

SN - 0006-2952

VL - 34

SP - 900

EP - 902

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

IS - 6

ER -