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Property "Has-20abstract" (as page type) with input value "-5B-5BImage:MITOEAGLE-2Dlogo.jpg-7Cleft-7C100px-7Clink=http:-2F-2Fwww.mitoglobal.org-2Findex.php-2FMITOEAGLE-7CCOST-20Action-20MitoEAGLE-5D-5D-0AMetabolic-20responses-20to-20hypoxia-20play-20important-20roles-20in-20both-20cell-20survival-20strategies-20and-20disease-20pathogenesis-20in-20humans.-20-20However,-20the-20homeostatic-20adjustments-20that-20balance-20changes-20in-20energy-20supply-20and-20demand-20to-20maintain-20organismal-20function-20under-20chronic-20low-20oxygen-20conditions-20remain-20incompletely-20understood,-20making-20it-20difficult-20to-20distinguish-20adaptive-20from-20maladaptive-20responses-20in-20hypoxia-2Drelated-20conditions.-20-20We-20integrated-20metabolomic-20and-20proteomic-20profiling-20with-20mitochondrial-20respirometry-20and-20blood-20gas-20analyses-20to-20comprehensively-20define-20the-20physiological-20responses-20of-20skeletal-20muscle-20energy-20metabolism-20to-2016-20days-20of-20high-2Daltitude-20hypoxia-20(5260-20m)-20in-20healthy,-20sedentary-20volunteers-20from-20the-202012-20AltitudeOmics-20expedition.-20-20In-20contrast-20to-20the-20view-20that-20hypoxia-20downregulates-20aerobic-20metabolism,-20results-20show-20that-20mitochondrial-20respiratory-20capacity-20is-20preserved-20following-20high-2Daltitude-20acclimatization,-20and-20plays-20a-20central-20role-20in-20adaptive-20responses-20by-20supporting-20higher-20resting-20phosphorylation-20potential-20and-20enhancing-20the-20efficiency-20of-20long-2Dchain-20acylcarnitine-20oxidation.-20-20This-20directs-20increases-20in-20muscle-20glucose-20towards-20pentose-20phosphate-20and-20one-2Dcarbon-20metabolism-20pathways-20that-20support-20cytosolic-20redox-20balance-20and-20help-20mitigate-20the-20effects-20of-20increased-20protein-20and-20purine-20nucleotide-20catabolism.-20-20Muscle-20accumulation-20of-20free-20amino-20acids-20supports-20these-20adjustments-20by-20coordinating-20cytosolic-20and-20mitochondrial-20pathways-20to-20rid-20the-20cell-20of-20excess-20nitrogen,-20but-20also-20leads-20to-20imbalances-20in-20citric-20acid-20cycle-20intermediates-20that-20might-20limit-20muscle-20oxidative-20capacity-20-27-27in-20vivo-27-27-20(e.g.,-20during-20exercise).-20-20Collectively,-20these-20studies-20illustrate-20how-20an-20integration-20of-20aerobic-20and-20anaerobic-20metabolism-20is-20required-20for-20adaptation-20of-20skeletal-20muscle-20to-20high-2Daltitude-20hypoxia.-20-20In-20addition,-20results-20highlight-20protein-20catabolism-20and-20allosteric-20regulation-20as-20unexpected-20orchestrators-20of-20metabolic-20remodeling-20at-20high-20altitude,-20rather-20that-20tissue-20hypoxia-20-27-27per-20se-27-27.-20These-20findings-20shed-20new-20light-20on-20how-20human-20skeletal-20muscle-20responds-20to-20metabolic-20stress,-20and-20may-20have-20important-20implications-20for-20the-20management-20of-20hypoxia-2Drelated-20diseases." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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