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Property "Has-20abstract" (as page type) with input value "Succinate-20dehydrogenase-20(SDH,-20mitochondrial-20Complex-20II)-20links-20the-20oxidation-20of-20succinate-20to-20fumarate-20and-20reduction-20of-20FAD-20to-20FADH2-20in-20the-20tricarboxylic-20acid-20(TCA)-20cycle.-20Further-20electron-20transfer-20(ET)-20proceeds-20from-20FADH2-20to-20ubiquinone-20in-20the-20ET-20system.-20Changes-20in-20ET-20capacity-20through-20the-20succinate-20pathway-20affect-20TCA-20cycle-20function-20and-20cell-20respiration.-20Succinate-20can-20accumulate-20in-20the-20mitochondria-20and-20be-20transported-20to-20the-20cytosol-20playing-20a-20role-20in-20stabilization-20of-20hypoxia-20inducible-20factor-201α,-20finally-20enabling-20tumour-20progression-20and-20metastasis.-20Succinate-20uptake-20is-20enhanced-20in-20various-20cancer-20cells-20and-20its-20mitochondrial-20utilisation-20is-20increased-20in-20permeabilized-20prostate-20cancer-20cells.-0ATo-20decipher-20the-20pathophysiological-20role-20of-20succinate-20in-20prostate-20cancer,-20we-20tested-20the-20utilization-20of-20external-20succinate-20by-20mitochondria-20in-20terms-20of-20succinate-20pathway-20capacity-20and-20kinetic-20properties-20in-20prostate-20cancer-20and-20control-20cell-20lines.-20Respiration-20in-20RWPE-2D1-20(noncancerous),-20LNCaP-20(lymph-20node-20metastasis)-20and-20DU145-20(brain-20metastasis)-20cells-20was-20measured-20using-20High-2DResolution-20FluoRespirometry-20(O2k,-20Oroboros-20Instruments)-20and-20substrate-2Duncoupler-2Dinhibitor-20titration-20(SUIT)-20protocols-20developed-20specifically-20for-20the-20study.-20To-20assess-20succinate-20utilization-20in-20intact-20cells-20independent-20of-20a-20plasma-20membrane-20succinate-20transporter,-20we-20applied-20novel-20plasma-20membrane-2Dpermeable-20succinate-20prodrugs-20(pS).-20-0AIn-20LNCaP-20cells,-20transport-20of-20external-20succinate-20is-20enhanced-20through-20the-20plasma-20membrane-20as-20compared-20to-20the-20other-20cell-20lines,-20while-20pS-20exerted-20similar-20effects-20in-20all-20cell-20lines,-20suggesting-20an-20important-20regulatory-20role-20of-20the-20transport-20mechanism.-20Furthermore,-20kinetic-20measurements-20demonstrated-20that-20in-20LNCaP-20cells,-20mitochondria-20utilize-20succinate-20with-20higher-20affinity-20than-20control-20cells,-20underlining-20its-20(patho)physiological-20role.-20Moreover,-20our-20results-20confirm-20that-20a-20lower-20extracellular-20pH-20can-20stimulate-20succinate-20utilization-20by-20mitochondria-20in-20LNCaP-20cells,-20possibly-20due-20to-20its-20interaction-20with-20the-20transporter,-20as-20previously-20described.-0AOur-20results-20indicate-20a-20“succinate-2Dphenotype”-20in-20LNCaP,-20with-20enhanced-20transport-20and-20utilization.-20As-20such,-20succinate-20is-20a-20potential-20mitochondrial-20metabolic-20biomarker-20in-20prostate-20cancer-20cells.-20We-20propose-20a-20model-20in-20which-20succinate-20does-20not-20only-20play-20a-20role-20in-20signalling-20but-20has-20a-20central-20role-20in-20the-20maintenance-20of-20mitochondrial-20respiration-20as-20a-20fuel-20substrate." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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