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Property "Has-20abstract" (as page type) with input value "The-20net-20emission-20of-20hydrogen-20peroxide-20H-3Csub-3E2-3C-2Fsub-3EO-3Csub-3E2-3C-2Fsub-3E-20from-20mitochondria-20results-20from-20the-20balance-20between-20reactive-20oxygen-20species-20(ROS)-20continuously-20generated-20in-20the-20respiratory-20chain-20and-20ROS-20scavenging.-20The-20relative-20contribution-20of-20the-20two-20major-20antioxidant-20systems-20in-20the-20mitochondrial-20matrix,-20glutathione-20(GSH)-20and-20thioredoxin-20(Trx),-20has-20not-20been-20assessed.-20In-20this-20paper,-20we-20examine-20this-20key-20question-20via-20combined-20experimental-20and-20theoretical-20approaches,-20using-20isolated-20heart-20mitochondria-20from-20mouse,-20rat,-20and-20guinea-20pig.-20As-20compared-20with-20untreated-20control-20mitochondria,-20selective-20inhibition-20of-20Trx-20reductase-20with-20auranofin-20along-20with-20depletion-20of-20GSH-20with-202,4-2Ddinitrochlorobenzene-20led-20to-20a-20species-2Ddependent-20increase-20in-20H-3Csub-3E2-3C-2Fsub-3EO-3Csub-3E2-3C-2Fsub-3E-20emission-20flux-20of-2017,-2011,-20and-206-20fold-20in-20state-204-20and-2015,-207,-20and-208-20fold-20in-20state-203-20for-20mouse,-20rat,-20and-20guinea-20pig-20mitochondria,-20respectively.-20The-20maximal-20H-3Csub-3E2-3C-2Fsub-3EO-3Csub-3E2-3C-2Fsub-3E-20emission-20as-20a-20percentage-20of-20the-20total-20O-3Csub-3E2-3C-2Fsub-3E-20consumption-20flux-20was-2011-25-2F2.3-25-20for-20mouse-20in-20states-204-20and-203-20followed-20by-202-25-2F0.25-25-20and-200.74-25-2F0.29-25-20in-20the-20rat-20and-20guinea-20pig,-20respectively.-20A-20minimal-20computational-20model-20accounting-20for-20the-20kinetics-20of-20GSH-2FTrx-20systems-20was-20developed-20and-20was-20able-20to-20simulate-20increase-20in-20H-3Csub-3E2-3C-2Fsub-3EO-3Csub-3E2-3C-2Fsub-3E-20emission-20fluxes-20when-20both-20scavenging-20systems-20were-20inhibited-20separately-20or-20together.-20Model-20simulations-20suggest-20that-20GSH-2FTrx-20systems-20act-20in-20concert.-20When-20the-20scavenging-20capacity-20of-20either-20one-20of-20them-20saturates-20during-20H-3Csub-3E2-3C-2Fsub-3EO-3Csub-3E2-3C-2Fsub-3E-20overload,-20they-20relieve-20each-20other-20until-20complete-20saturation,-20when-20maximal-20ROS-20emission-20occurs.-20Quantitatively,-20these-20results-20converge-20on-20the-20idea-20that-20GSH-2FTrx-20scavenging-20systems-20in-20mitochondria-20are-20both-20essential-20for-20keeping-20minimal-20levels-20of-20H-3Csub-3E2-3C-2Fsub-3EO-3Csub-3E2-3C-2Fsub-3E-20emission,-20especially-20during-20state-203-20respiration,-20when-20the-20energetic-20output-20is-20maximal.-20This-20suggests-20that-20the-20very-20low-20levels-20of-20H-3Csub-3E2-3C-2Fsub-3EO-3Csub-3E2-3C-2Fsub-3E-20emission-20observed-20during-20forward-20electron-20transport-20in-20the-20respiratory-20chain-20are-20a-20result-20of-20the-20well-2Dorchestrated-20actions-20of-20the-20two-20antioxidant-20systems-20working-20continuously-20to-20offset-20ROS-20production." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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