{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:20:15Z","timestamp":1790828415607,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T00:00:00Z","timestamp":1779580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T00:00:00Z","timestamp":1779580800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"\n Abstract<\/jats:title>\n \n Mitochondrial oxygen (O\n 2<\/jats:sub>\n ) affinity is a fundamental determinant of oxidative phosphorylation capacity, which has yet to be directly measured in human skeletal muscle\n in vivo<\/jats:italic>\n . To determine the apparent mitochondrial O\n 2<\/jats:sub>\n affinity (i.e.\n P<\/jats:italic>\n 50<\/jats:sub>\n ) of the skeletal muscle, we used proton\u2010magnetic resonance spectroscopy (\n 1<\/jats:sup>\n H\u2010MRS) of deoxymyoglobin (dMb) during a circulatory occlusion of the lower limb to simultaneously quantify intracellular partial pressure of O\n 2<\/jats:sub>\n (i ) and resting tissue\u2010specific O\n 2<\/jats:sub>\n consumption () in the gastrocnemius muscle of sedentary young adults. Under these resting conditions, the \u2013i relationship conformed to a Michaelis\u2013Menten kinetics model (goodness of fit:\n r<\/jats:italic>\n 2<\/jats:sup>\n \u00a0=\u00a00.84\u00a0\u00b1\u00a00.13). The estimated\n V<\/jats:italic>\n ss<\/jats:sub>\n , reflecting basal metabolic rate, reached 0.20\u00a0\u00b1\u00a00.06\u00a0mM\u00a0min\n \u22121<\/jats:sup>\n , and the apparent mitochondrial\n P<\/jats:italic>\n 50<\/jats:sub>\n was 0.50\u00a0\u00b1\u00a00.38\u00a0mmHg.\n V<\/jats:italic>\n ss<\/jats:sub>\n and\n P<\/jats:italic>\n 50<\/jats:sub>\n were positively correlated (\n r<\/jats:italic>\n \u00a0=\u00a00.85,\n P<\/jats:italic>\n \u00a0=\u00a00.0009). This strong correlation remained after log transformation (\n r<\/jats:italic>\n \u00a0=\u00a00.82,\n P<\/jats:italic>\n \u00a0=\u00a00.0020). These results, obtained in human muscles\n in vivo<\/jats:italic>\n , demonstrate that mitochondrial respiration exhibits a very high O\n 2<\/jats:sub>\n affinity (\n P<\/jats:italic>\n 50<\/jats:sub>\n \u00a0\u2248\u00a00.5\u00a0mmHg). In addition, it quantitatively identifies the range across which oxidative phosphorylation in the skeletal muscle is O\n 2<\/jats:sub>\n \u2010independent (resting i under physiological conditions) or becomes O\n 2<\/jats:sub>\n \u2010sensitive (severe exercise and hypoxia). Moreover, the finding that muscle respiratory flux was associated with the apparent mitochondrial O\n 2<\/jats:sub>\n affinity suggests additional regulatory mechanisms within the respiratory chain to fine\u2010tune oxidative phosphorylation to muscle ATP demand even at rest. This study provides a robust quantitative framework for interpreting\n in vivo<\/jats:italic>\n respiratory control in both health and disease.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n Mitochondrial oxygen affinity (\n P<\/jats:italic>\n 50<\/jats:sub>\n ) is central to oxidative phosphorylation, yet has not been directly quantified in human skeletal muscle\n in vivo<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:list-item>\n \n \n Using deoxymyoglobin\n 1<\/jats:sup>\n H\u2010MRS during 8\u00a0min of lower\u2010limb ischaemia, we simultaneously measure intracellular partial pressure of O\n 2<\/jats:sub>\n (i ) and resting tissue\u2010specific O\n 2<\/jats:sub>\n consumption () in the resting gastrocnemius of healthy young adults.\n <\/jats:p>\n <\/jats:list-item>\n \n \n The \u2013 relationship followed Michaelis\u2013Menten kinetics, yielding a\n V<\/jats:italic>\n ss<\/jats:sub>\n of 0.20\u00a0mM\u00a0min\n \u22121<\/jats:sup>\n and an apparent mitochondrial\n P<\/jats:italic>\n 50<\/jats:sub>\n of 0.50\u00a0mmHg, indicating very high O\n 2<\/jats:sub>\n affinity.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Resting apparent mitochondrial\n P<\/jats:italic>\n 50<\/jats:sub>\n was far below previously reported i (\u223c34\u00a0mmHg), indicating a wide O\n 2<\/jats:sub>\n \u2010independent range and identifying conditions (severe hypoxia, high\u2010intensity exercise) in which oxidative phosphorylation becomes O\n 2<\/jats:sub>\n \u2010sensitive.\n <\/jats:p>\n <\/jats:list-item>\n \n \n V<\/jats:italic>\n ss<\/jats:sub>\n and\n P<\/jats:italic>\n 50<\/jats:sub>\n were positively correlated (\n r<\/jats:italic>\n \u00a0=\u00a00.85), suggesting\n in vivo<\/jats:italic>\n coupling between respiratory flux and oxygen affinity and providing a potential quantitative framework for interpreting mitochondrial respiratory control in health and disease.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp290548","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T01:10:00Z","timestamp":1779671400000},"page":"4876-4888","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In vivo<\/i>\n quantification of mitochondrial O\n 2<\/sub>\n affinity in human skeletal muscle using\n 1<\/sup>\n H\u2010magnetic resonance spectroscopy of deoxy\u2010myoglobin"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1037-7399","authenticated-orcid":false,"given":"Muhammet Enes","family":"Erol","sequence":"first","affiliation":[{"name":"Department of Kinesiology and Institute for Applied Life Sciences University of Massachusetts Amherst Amherst Massachusetts USA"},{"name":"School of Health and Kinesiology University of Nebraska Omaha Omaha Nebraska 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