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The aim of this study was to evaluate mitochondrial sensitivity to submaximal [ADP] by an alternative approach aimed at identifying responses associated with fibre type composition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Isolated permeabilized <jats:italic>vastus lateralis<\/jats:italic> fibres were analysed by high\u2010resolution respirometry in 9 young males before and after a 10\u2010day horizontal bed rest. Eleven submaximal titrations of ADP (from 12.5 to 10\u2009000\u2009\u03bcM) were utilized to assess complex I\u2009+\u2009II\u2010linked ADP sensitivity. We applied to JO<jats:sub>2<\/jats:sub> versus [ADP] data a traditional Michaelis\u2013Menten kinetics equation, with the calculation of the apparent K<jats:sub>m<\/jats:sub> and maximal respiration (V<jats:sub>max<\/jats:sub>), and two \u2018sequential\u2019 hyperbolic equations, yielding two K<jats:sub>m<\/jats:sub> and V<jats:sub>max<\/jats:sub> values. The two\u2010hyperbolic equations were solved and the [ADP] value corresponding to 50% of JO<jats:sub>2max<\/jats:sub> was calculated. Isoform expression of myosin heavy chains (MyHC) 1, 2A and 2X was also determined. Control experiments were also carried out on rat skeletal muscle samples with different percentages of MyHC isoforms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The two hyperbolic equations provided an alternative fitting of data and identified two distinct phases of the JO<jats:sub>2<\/jats:sub> versus [ADP] response: a first phase characterized by low V<jats:sub>max<\/jats:sub> (V<jats:sub>max1<\/jats:sub>, 28\u2009\u00b1\u200910\u2009pmol s<jats:sup>\u22121<\/jats:sup> mg<jats:sup>\u22121<\/jats:sup>) and apparent K<jats:sub>m<\/jats:sub> (K<jats:sub>m1<\/jats:sub>, 62\u2009\u00b1\u200954\u2009\u03bcM) and a second phase characterized by higher V<jats:sub>max<\/jats:sub> (V<jats:sub>max2<\/jats:sub>, 61\u2009\u00b1\u200916\u2009pmol s<jats:sup>\u22121<\/jats:sup> mg<jats:sup>\u22121<\/jats:sup>) and K<jats:sub>m<\/jats:sub> (K<jats:sub>m2<\/jats:sub>, 1784\u2009\u00b1\u2009833\u2009\u03bcM). Data were confirmed in control experiments carried out in rat muscle samples with different percentages of MyHC isoforms. Correlation and receiver operating characteristics analyses suggest that the two phases of the response were related to the % of MyHC isoforms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A novel mathematical approach (two sequential hyperbolic functions) for the fitting of JO<jats:sub>2<\/jats:sub> versus [ADP] data obtained by high\u2010resolution respirometry on permeabilized skeletal muscle fibres, obtained in humans and rats, provided an alternative fitting of the experimental data compared to the traditional Michaelis\u2013Menten kinetics equation. This alternative model allowed the identification of two distinct phases in the responses, which were related to fibre type composition. A first phase, characterized by low apparent K<jats:sub>m<\/jats:sub> and V<jats:sub>max<\/jats:sub> values, was correlated with the percentage of less oxidative (Type 2A\u2009+\u20092X) MyHC isoforms. A second phase, characterized by high apparent K<jats:sub>m<\/jats:sub> and V<jats:sub>max<\/jats:sub>, was related to more oxidative (Type 1) MyHC isoforms.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13775","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T05:39:21Z","timestamp":1745645961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mitochondrial Sensitivity to Submaximal [ADP] Following Bed Rest: A Novel Two\u2010Phase Approach Associated With Fibre Types"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2447-4684","authenticated-orcid":false,"given":"Lucrezia","family":"Zuccarelli","sequence":"first","affiliation":[{"name":"Department of Medicine University of Udine  Udine 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