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Property "Has-20abstract" (as page type) with input value "Excess-20reactive-20oxygen-20species-20(ROS)-20and-20muscle-20weakness-20occur-20in-20parallel-20in-20multiple-20pathological-20conditions.-20However,-20the-20causative-20role-20of-20skeletal-20muscle-20mitochondrial-20ROS-20(mtROS)-20on-20neuromuscular-20junction-20(NMJ)-20morphology-20and-20function-20and-20muscle-20weakness-20has-20not-20been-20directly-20investigated.-0A-0AWe-20generated-20mice-20lacking-20skeletal-20muscle-2Dspecific-20manganese-2Dsuperoxide-20dismutase-20(mSod2KO)-20to-20increase-20mtROS-20using-20a-20cre-2DLox-20approach-20driven-20by-20human-20skeletal-20actin.-20We-20determined-20primary-20functional-20parameters-20of-20skeletal-20muscle-20mitochondrial-20function-20(respiration,-20ROS,-20and-20calcium-20retention-20capacity)-20using-20permeabilized-20muscle-20fibers-20and-20isolated-20muscle-20mitochondria.-20We-20assessed-20contractile-20properties-20of-20isolated-20skeletal-20muscle-20using-20-27-27in-20situ-27-27-20and-20-27-27in-20vitro-27-27-20preparations-20and-20whole-20lumbrical-20muscles-20to-20elucidate-20the-20mechanisms-20of-20contractile-20dysfunction.-0A-0AThe-20mSod2KO-20mice,-20contrary-20to-20our-20prediction,-20exhibit-20a-2010-2D15-25-20increase-20in-20muscle-20mass-20associated-20with-20an-20~50-25-20increase-20in-20central-20nuclei-20and-20~35-25-20increase-20in-20branched-20fibers-20(P-20-3C-200.05).-20Despite-20the-20increase-20in-20muscle-20mass-20of-20-27-27gastrocnemius-27-27-20and-20-27-27quadriceps-27-27,-20in-20situ-20sciatic-20nerve-2Dstimulated-20isometric-20maximum-2Dspecific-20force-20(N-2Fcm-3Csup-3E2-3C-2Fsup-3E),-20force-20per-20cross-2Dsectional-20area,-20is-20impaired-20by-20~60-25-20and-20associated-20with-20increased-20NMJ-20fragmentation-20and-20size-20by-20~40-25-20(P-20-3C-200.05).-20Intrinsic-20alterations-20of-20components-20of-20the-20contractile-20machinery-20show-20elevated-20markers-20of-20oxidative-20stress,-20for-20example,-20lipid-20peroxidation-20is-20increased-20by-20~100-25,-20oxidized-20glutathione-20is-20elevated-20by-20~50-25,-20and-20oxidative-20modifications-20of-20myofibrillar-20proteins-20are-20increased-20by-20~30-25-20(P-20-3C-200.05).-20We-20also-20find-20an-20approximate-2020-25-20decrease-20in-20the-20intracellular-20calcium-20transient-20that-20is-20associated-20with-20specific-20force-20deficit.-20Excess-20superoxide-20generation-20from-20the-20mitochondrial-20complexes-20causes-20a-20deficiency-20of-20succinate-20dehydrogenase-20and-20reduced-20complex-2DII-2Dmediated-20respiration-20and-20adenosine-20triphosphate-20generation-20rates-20leading-20to-20severe-20exercise-20intolerance-20(~10-20min-20vs.-20~2-20h-20in-20wild-20type,-20P-20-3C-200.05).-0A-0AIncreased-20skeletal-20muscle-20mtROS-20is-20sufficient-20to-20elicit-20NMJ-20disruption-20and-20contractile-20abnormalities,-20but-20not-20muscle-20atrophy,-20suggesting-20new-20roles-20for-20mitochondrial-20oxidative-20stress-20in-20maintenance-20of-20muscle-20mass-20through-20increased-20fiber-20branching.-0A-0A-3Csmall-3E©-202019-20The-20Authors.-20Journal-20of-20Cachexia,-20Sarcopenia-20and-20Muscle-20published-20by-20John-20Wiley-20-26-20Sons-20Ltd-20on-20behalf-20of-20the-20Society-20on-20Sarcopenia,-20Cachexia-20and-20Wasting-20Disorders.-3C-2Fsmall-3E" contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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