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Chicco 2018 J Biol Chem - Revision history
2024-03-28T10:02:42Z
Revision history for this page on the wiki
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https://wiki.oroboros.at/index.php?title=Chicco_2018_J_Biol_Chem&diff=223133&oldid=prev
Gnaiger Erich at 10:50, 27 December 2021
2021-12-27T10:50:26Z
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<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">== Cited by ==</ins></div></td></tr>
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Gnaiger Erich
https://wiki.oroboros.at/index.php?title=Chicco_2018_J_Biol_Chem&diff=222452&oldid=prev
Gnaiger Erich at 09:08, 27 November 2021
2021-11-27T09:08:53Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 09:08, 27 November 2021</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|journal=J Biol Chem</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|journal=J Biol Chem</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|abstract=Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from maladaptive responses in hypoxia-related pathologies. We integrated metabolomic and proteomic profiling with mitochondrial respirometry and blood gas analyses to comprehensively define the physiological responses of skeletal muscle energy metabolism to 16 days of high-altitude hypoxia (5260 m) in healthy volunteers from the AltitudeOmics project. In contrast to the view that hypoxia downregulates aerobic metabolism, results show that mitochondria play a central role in muscle hypoxia adaptation by supporting higher resting phosphorylation potential and enhancing the efficiency of long-chain acylcarnitine oxidation. This directs increases in muscle glucose towards pentose phosphate and one-carbon metabolism pathways that support cytosolic redox balance and help mitigate the effects of increased protein and purine nucleotide catabolism in hypoxia. Muscle accumulation of free amino acids favor these adjustments by coordinating cytosolic and mitochondrial pathways to rid the cell of excess nitrogen, but might ultimately limit muscle oxidative capacity ''in vivo''. Collectively, these studies illustrate how an integration of aerobic and anaerobic metabolism is required for physiological hypoxia adaptation in skeletal muscle, and highlight protein catabolism and allosteric regulation as unexpected orchestrators of metabolic remodeling in this context. These findings have important implications for the management of hypoxia-related diseases and other conditions associated with chronic catabolic stress.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|abstract=Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from maladaptive responses in hypoxia-related pathologies. We integrated metabolomic and proteomic profiling with mitochondrial respirometry and blood gas analyses to comprehensively define the physiological responses of skeletal muscle energy metabolism to 16 days of high-altitude hypoxia (5260 m) in healthy volunteers from the AltitudeOmics project. In contrast to the view that hypoxia downregulates aerobic metabolism, results show that mitochondria play a central role in muscle hypoxia adaptation by supporting higher resting phosphorylation potential and enhancing the efficiency of long-chain acylcarnitine oxidation. This directs increases in muscle glucose towards pentose phosphate and one-carbon metabolism pathways that support cytosolic redox balance and help mitigate the effects of increased protein and purine nucleotide catabolism in hypoxia. Muscle accumulation of free amino acids favor these adjustments by coordinating cytosolic and mitochondrial pathways to rid the cell of excess nitrogen, but might ultimately limit muscle oxidative capacity ''in vivo''. Collectively, these studies illustrate how an integration of aerobic and anaerobic metabolism is required for physiological hypoxia adaptation in skeletal muscle, and highlight protein catabolism and allosteric regulation as unexpected orchestrators of metabolic remodeling in this context. These findings have important implications for the management of hypoxia-related diseases and other conditions associated with chronic catabolic stress.</div></td></tr>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|keywords=Anaplerosis, Beta-oxidation, Bioenergetics, Fatty acid oxidation, Glycolysis, Hypoxia, Mitochondrial metabolism, One-carbon metabolism, Oxidation-reduction (redox)</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|keywords=Anaplerosis, Beta-oxidation, Bioenergetics, Fatty acid oxidation, Glycolysis, Hypoxia, Mitochondrial metabolism, One-carbon metabolism, Oxidation-reduction (redox)</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|editor=[[Kandolf G]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|editor=[[Kandolf G]]</div></td></tr>
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Gnaiger Erich
https://wiki.oroboros.at/index.php?title=Chicco_2018_J_Biol_Chem&diff=222173&oldid=prev
Gnaiger Erich at 01:22, 23 November 2021
2021-11-23T01:22:32Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 01:22, 23 November 2021</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|title=Chicco AJ, Le CH, Gnaiger E, Dreyer HC, Muyskens JB, D'Alessandro A, Nemkov T, Hocker AD, Prenni JE, Wolfe LM, Sindt NM, Lovering AT, Subudhi AW, Roach RC (2018) Adaptive remodeling of skeletal muscle energy metabolism in high-altitude hypoxia: Lessons from AltitudeOmics. J Biol Chem 293:6659-71.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|title=Chicco AJ, Le CH, Gnaiger E, Dreyer HC, Muyskens JB, D'Alessandro A, Nemkov T, Hocker AD, Prenni JE, Wolfe LM, Sindt NM, Lovering AT, Subudhi AW, Roach RC (2018) Adaptive remodeling of skeletal muscle energy metabolism in high-altitude hypoxia: Lessons from AltitudeOmics. J Biol Chem 293:6659-71.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://www.ncbi.nlm.nih.gov/pubmed/29540485 PMID: 29540485 Open Access]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://www.ncbi.nlm.nih.gov/pubmed/29540485 PMID: 29540485 Open Access]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>|authors=Chicco AJ, Le CH, Gnaiger <del style="font-weight: bold; text-decoration: none;">E</del>, Dreyer HC, Muyskens JB, D'Alessandro A, Nemkov T, Hocker AD, Prenni JE, Wolfe LM, Sindt NM, Lovering AT, Subudhi AW, Roach RC</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>|authors=Chicco AJ, Le CH, Gnaiger <ins style="font-weight: bold; text-decoration: none;">Erich</ins>, Dreyer HC, Muyskens JB, D'Alessandro A, Nemkov T, Hocker AD, Prenni JE, Wolfe LM, Sindt NM, Lovering AT, Subudhi AW, Roach RC</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|year=2018</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|year=2018</div></td></tr>
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Gnaiger Erich
https://wiki.oroboros.at/index.php?title=Chicco_2018_J_Biol_Chem&diff=192401&oldid=prev
Gnaiger Erich at 16:43, 10 February 2020
2020-02-10T16:43:52Z
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|area=Respiration, Exercise physiology;nutrition;life style, mt-Medicine</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|area=Respiration, Exercise physiology;nutrition;life style, mt-Medicine</div></td></tr>
</table>
Gnaiger Erich
https://wiki.oroboros.at/index.php?title=Chicco_2018_J_Biol_Chem&diff=163502&oldid=prev
Gnaiger Erich at 07:00, 5 October 2018
2018-10-05T07:00:16Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 07:00, 5 October 2018</td>
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<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>|title=Chicco AJ, Le CH, Gnaiger E, Dreyer HC, Muyskens JB, D'Alessandro A, Nemkov T, Hocker AD, Prenni JE, Wolfe LM, Sindt NM, Lovering AT, Subudhi AW, Roach RC (2018) Adaptive remodeling of skeletal muscle energy metabolism in high-altitude hypoxia: Lessons from AltitudeOmics. J Biol Chem <del style="font-weight: bold; text-decoration: none;">[Epub ahead of print]</del>.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>|title=Chicco AJ, Le CH, Gnaiger E, Dreyer HC, Muyskens JB, D'Alessandro A, Nemkov T, Hocker AD, Prenni JE, Wolfe LM, Sindt NM, Lovering AT, Subudhi AW, Roach RC (2018) Adaptive remodeling of skeletal muscle energy metabolism in high-altitude hypoxia: Lessons from AltitudeOmics. J Biol Chem <ins style="font-weight: bold; text-decoration: none;">293:6659-71</ins>.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://www.ncbi.nlm.nih.gov/pubmed/29540485 PMID: 29540485 Open Access]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://www.ncbi.nlm.nih.gov/pubmed/29540485 PMID: 29540485 Open Access]</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|authors=Chicco AJ, Le CH, Gnaiger E, Dreyer HC, Muyskens JB, D'Alessandro A, Nemkov T, Hocker AD, Prenni JE, Wolfe LM, Sindt NM, Lovering AT, Subudhi AW, Roach RC</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|authors=Chicco AJ, Le CH, Gnaiger E, Dreyer HC, Muyskens JB, D'Alessandro A, Nemkov T, Hocker AD, Prenni JE, Wolfe LM, Sindt NM, Lovering AT, Subudhi AW, Roach RC</div></td></tr>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|journal=J Biol Chem</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|journal=J Biol Chem</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>|abstract=Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from maladaptive responses in hypoxia-related pathologies. <del style="font-weight: bold; text-decoration: none;"> </del>We integrated metabolomic and proteomic profiling with mitochondrial respirometry and blood gas analyses to comprehensively define the physiological responses of skeletal muscle energy metabolism to 16 days of high-altitude hypoxia (5260 m) in healthy volunteers from the AltitudeOmics project. <del style="font-weight: bold; text-decoration: none;"> </del>In contrast to the view that hypoxia downregulates aerobic metabolism, results show that mitochondria play a central role in muscle hypoxia adaptation by supporting higher resting phosphorylation potential and enhancing the efficiency of long-chain acylcarnitine oxidation. <del style="font-weight: bold; text-decoration: none;"> </del>This directs increases in muscle glucose towards pentose phosphate and one-carbon metabolism pathways that support cytosolic redox balance and help mitigate the effects of increased protein and purine nucleotide catabolism in hypoxia. <del style="font-weight: bold; text-decoration: none;"> </del>Muscle accumulation of free amino acids favor these adjustments by coordinating cytosolic and mitochondrial pathways to rid the cell of excess nitrogen, but might ultimately limit muscle oxidative capacity ''in vivo''. Collectively, these studies illustrate how an integration of aerobic and anaerobic metabolism is required for physiological hypoxia adaptation in skeletal muscle, and highlight protein catabolism and allosteric regulation as unexpected orchestrators of metabolic remodeling in this context. <del style="font-weight: bold; text-decoration: none;"> </del>These findings have important implications for the management of hypoxia-related diseases and other conditions associated with chronic catabolic stress.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>|abstract=Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from maladaptive responses in hypoxia-related pathologies. We integrated metabolomic and proteomic profiling with mitochondrial respirometry and blood gas analyses to comprehensively define the physiological responses of skeletal muscle energy metabolism to 16 days of high-altitude hypoxia (5260 m) in healthy volunteers from the AltitudeOmics project. In contrast to the view that hypoxia downregulates aerobic metabolism, results show that mitochondria play a central role in muscle hypoxia adaptation by supporting higher resting phosphorylation potential and enhancing the efficiency of long-chain acylcarnitine oxidation. This directs increases in muscle glucose towards pentose phosphate and one-carbon metabolism pathways that support cytosolic redox balance and help mitigate the effects of increased protein and purine nucleotide catabolism in hypoxia. Muscle accumulation of free amino acids favor these adjustments by coordinating cytosolic and mitochondrial pathways to rid the cell of excess nitrogen, but might ultimately limit muscle oxidative capacity ''in vivo''. Collectively, these studies illustrate how an integration of aerobic and anaerobic metabolism is required for physiological hypoxia adaptation in skeletal muscle, and highlight protein catabolism and allosteric regulation as unexpected orchestrators of metabolic remodeling in this context. These findings have important implications for the management of hypoxia-related diseases and other conditions associated with chronic catabolic stress.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|keywords=Anaplerosis, Beta-oxidation, Bioenergetics, Fatty acid oxidation, Glycolysis, Hypoxia, Mitochondrial metabolism, One-carbon metabolism, Oxidation-reduction (redox)</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|keywords=Anaplerosis, Beta-oxidation, Bioenergetics, Fatty acid oxidation, Glycolysis, Hypoxia, Mitochondrial metabolism, One-carbon metabolism, Oxidation-reduction (redox)</div></td></tr>
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</table>
Gnaiger Erich
https://wiki.oroboros.at/index.php?title=Chicco_2018_J_Biol_Chem&diff=157899&oldid=prev
Krumschnabel Gerhard at 07:46, 28 May 2018
2018-05-28T07:46:09Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 07:46, 28 May 2018</td>
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<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>|area=Respiration, mt-Medicine</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>|area=Respiration<ins style="font-weight: bold; text-decoration: none;">, Exercise physiology;nutrition;life style</ins>, mt-Medicine</div></td></tr>
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</table>
Krumschnabel Gerhard
https://wiki.oroboros.at/index.php?title=Chicco_2018_J_Biol_Chem&diff=154852&oldid=prev
Kandolf Georg: Created page with "{{Publication |title=Chicco AJ, Le CH, Gnaiger E, Dreyer HC, Muyskens JB, D'Alessandro A, Nemkov T, Hocker AD, Prenni JE, Wolfe LM, Sindt NM, Lovering AT, Subudhi AW, Roach RC..."
2018-03-20T13:29:17Z
<p>Created page with "{{Publication |title=Chicco AJ, Le CH, Gnaiger E, Dreyer HC, Muyskens JB, D'Alessandro A, Nemkov T, Hocker AD, Prenni JE, Wolfe LM, Sindt NM, Lovering AT, Subudhi AW, Roach RC..."</p>
<p><b>New page</b></p><div>{{Publication<br />
|title=Chicco AJ, Le CH, Gnaiger E, Dreyer HC, Muyskens JB, D'Alessandro A, Nemkov T, Hocker AD, Prenni JE, Wolfe LM, Sindt NM, Lovering AT, Subudhi AW, Roach RC (2018) Adaptive remodeling of skeletal muscle energy metabolism in high-altitude hypoxia: Lessons from AltitudeOmics. J Biol Chem [Epub ahead of print].<br />
|info=[https://www.ncbi.nlm.nih.gov/pubmed/29540485 PMID: 29540485 Open Access]<br />
|authors=Chicco AJ, Le CH, Gnaiger E, Dreyer HC, Muyskens JB, D'Alessandro A, Nemkov T, Hocker AD, Prenni JE, Wolfe LM, Sindt NM, Lovering AT, Subudhi AW, Roach RC<br />
|year=2018<br />
|journal=J Biol Chem<br />
|abstract=Metabolic responses to hypoxia play important roles in cell survival strategies and disease pathogenesis in humans. However, the homeostatic adjustments that balance changes in energy supply and demand to maintain organismal function under chronic low oxygen conditions remain incompletely understood, making it difficult to distinguish adaptive from maladaptive responses in hypoxia-related pathologies. We integrated metabolomic and proteomic profiling with mitochondrial respirometry and blood gas analyses to comprehensively define the physiological responses of skeletal muscle energy metabolism to 16 days of high-altitude hypoxia (5260 m) in healthy volunteers from the AltitudeOmics project. In contrast to the view that hypoxia downregulates aerobic metabolism, results show that mitochondria play a central role in muscle hypoxia adaptation by supporting higher resting phosphorylation potential and enhancing the efficiency of long-chain acylcarnitine oxidation. This directs increases in muscle glucose towards pentose phosphate and one-carbon metabolism pathways that support cytosolic redox balance and help mitigate the effects of increased protein and purine nucleotide catabolism in hypoxia. Muscle accumulation of free amino acids favor these adjustments by coordinating cytosolic and mitochondrial pathways to rid the cell of excess nitrogen, but might ultimately limit muscle oxidative capacity ''in vivo''. Collectively, these studies illustrate how an integration of aerobic and anaerobic metabolism is required for physiological hypoxia adaptation in skeletal muscle, and highlight protein catabolism and allosteric regulation as unexpected orchestrators of metabolic remodeling in this context. These findings have important implications for the management of hypoxia-related diseases and other conditions associated with chronic catabolic stress.<br />
|keywords=Anaplerosis, Beta-oxidation, Bioenergetics, Fatty acid oxidation, Glycolysis, Hypoxia, Mitochondrial metabolism, One-carbon metabolism, Oxidation-reduction (redox)<br />
|editor=[[Kandolf G]]<br />
|mipnetlab=US CO Fort Collins Chicco AJ, AT Innsbruck Gnaiger E, AT Innsbruck Oroboros<br />
}}<br />
{{Labeling<br />
|area=Respiration, mt-Medicine<br />
|injuries=Hypoxia<br />
|organism=Human<br />
|tissues=Skeletal muscle<br />
|preparations=Permeabilized tissue<br />
|couplingstates=LEAK, OXPHOS, ET<br />
|pathways=F, N, S<br />
|instruments=Oxygraph-2k<br />
|additional=Labels, 2018-03<br />
}}</div>
Kandolf Georg