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"Has-20abstract%2FOxygen-20consumption-20by-20isolated-20mitochondria-20is-20generally-20measured-20during-20state-204-20respiration-20%28no-20ATP-20production%29-20or-20state-203-20%28maximal-20ATP-20production-20at-20high-20ADP-20availability%29.-20However%2C-20mitochondria-20-27-27in-20vivo-27-27-20do-20not-20function-20at-20either-20extreme.-20Here-20we-20used-20ADP-20recycling-20methodology-20to-20assess-20muscle-20mitochondrial-20function-20over-20intermediate-20clamped-20ADP-20concentrations.-20In-20so-20doing%2C-20we-20uncovered-20a-20previously-20unrecognized-20biphasic-20respiratory-20pattern-20wherein-20O-3Csub-3E2-3C-2Fsub-3E-20flux-20on-20the-20complex-20II-20substrate%2C-20succinate%2C-20initially-20increased-20and-20peaked-20over-20low-20clamped-20ADP-20concentrations-20then-20decreased-20markedly-20at-20higher-20clamped-20concentrations.-20Mechanistic-20studies-20revealed-20no-20evidence-20that-20the-20observed-20changes-20in-20O-3Csub-3E2-3C-2Fsub-3E-20flux-20were-20due-20to-20altered-20opening-20or-20function-20of-20the-20mitochondrial-20permeability-20transition-20pore-20or-20to-20changes-20in-20reactive-20oxygen.-20Based-20on-20metabolite-20and-20functional-20metabolic-20data%2C-20we-20propose-20a-20multifactorial-20mechanism-20that-20consists-20of-20coordinate-20changes-20that-20follow-20from-20reduced-20membrane-20potential-20%28as-20the-20ADP-20concentration-20in-20increased%29.-20These-20changes-20include-20altered-20directional-20electron-20flow%2C-20altered-20NADH-2FNAD-3Csup-3E%2B-3C-2Fsup-3E-20redox-20cycling%2C-20metabolite-20exit%2C-20and-20OAA-20inhibition-20of-20succinate-20dehydrogenase.-20In-20summary%2C-20we-20report-20a-20previously-20unrecognized-20pattern-20for-20complex-20II-20energized-20O-3Csub-3E2-3C-2Fsub-3E-20flux.-20Moreover%2C-20our-20findings-20suggest-20that-20the-20ADP-20recycling-20approach-20might-20be-20more-20widely-20adapted-20for-20mitochondrial-20studies" contains a listed "%" character as part of the property label and has therefore been classified as invalid.

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