{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:19:19Z","timestamp":1791584359153,"version":"4.3.4"},"reference-count":91,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Exercise stimulates skeletal muscle signalling and mitochondrial metabolism. Emerging evidence shows that mitochondrial dynamics (i.e. fission and fusion) could be regulated by exercise. Yet, key gaps remain in identifying (i) the signals that drive fission\n                      <jats:italic>vs<\/jats:italic>\n                      . fusion; (ii) how energy status and reactive oxygen species (ROS) shift control between dynamin\u2010related protein 1 (DRP1) and mitofusin (MFN)\/optic atrophy 1 (OPA1); and (iii) which intensity\u2013duration combinations yield similar cytosolic signals but different mitochondrial remodelling. Therefore, we developed an integrative computational framework connecting exercise regimens to mitochondria fission\u2013fusion machinery by linking blood\u2013myofibre energetics in cytosol and mitochondria to signalling pathways. The influence of sprint, resistance and endurance exercise regimens on mitochondrial fission and fusion has been simulated. Classified qualitative validation of the signalling network model achieved 80% accuracy. The model predicts regimen\u2010specific dynamics starting with an acute DRP1\u2010driven fission during exercise followed by MFN1\/2\u2013OPA1\u2010mediated re\u2010fusion as energy stress declines, consistent with a cyclical triage\u2010then\u2010rebuild paradigm. Changes are most pronounced and sustained with endurance, sharp but brief with sprint, and minimal with resistance. Global sensitivity analysis identified AMP\u2010activated protein kinase (AMPK)\/peroxisome proliferator\u2010activated receptor gamma coactivator\u20101\u03b1\u2192MFN1\/2 as dominant fusion drivers, ROS and AMPK\u2192mitochondrial fission factor\/DRP1 as primary fission switches, and Ca\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sup>+<\/jats:sup>\n                      \u2013calmodulin, extracellular\u2010signal\u2010regulated kinase and liver kinase B1\/AMPK as shared regulators. The model predicts that an endurance base, augmented with one or two weekly high intensity interval training\/sprint interval training sessions could maximize AMPK\u2013ROS pulses and mitochondrial fission\u2013fusion. This framework unifies muscle's signalling logic with energetic state to explain how intensity\u2013volume combinations, bout spacing and kinase modulation tune mitochondrial remodelling, yielding testable predictions for optimizing training and adjuvant therapies to enhance mitochondrial quality and performance.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70664-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Different exercise regimes such as sprint, resistance, and endurance can trigger different signalling pathways.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Exercise also triggers mitochondrial remodelling in skeletal muscle.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Using a systems biology model, we developed a systems biology model for skeletal muscle signalling and mitochondrial metabolism for exercise.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our model predicts the dynamics of mitochondrial fusion and fission in different exercise regimes and identifies which signalling pathways dominassste these remodelling mechanisms.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp290424","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:15:39Z","timestamp":1782936939000},"page":"6369-6390","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Systems modelling of mitochondrial dynamics in different exercise regimes"],"prefix":"10.1113","volume":"604","author":[{"given":"Ali","family":"Khalilimeybodi","sequence":"first","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering University of California  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxia","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California San Diego  La Jolla CA 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