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Biol."],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>ATP is the major energy source for myotube contraction, and is quickly produced to compensate ATP consumption and to maintain sufficient ATP level. ATP is consumed mainly in cytoplasm and produced in mitochondria during myotube contraction. To understand the mechanism of ATP homeostasis during myotube contraction, it is essential to monitor mitochondrial ATP at single\u2010cell level, and examine how ATP is produced and consumed in mitochondria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established C2C12 cell line stably expressing fluorescent probe of mitochondrial ATP, and induced differentiation into myotubes. We gave electric pulse stimulation to the differentiated myotubes, and measured mitochondrial ATP. We constructed mathematical model of mitochondrial ATP at single\u2010cell level, and analyzed kinetic parameters of ATP production and consumption.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We performed hierarchical clustering analysis of time course of mitochondrial ATP, which resulted in two clusters. Cluster 1 showed strong transient increase, whereas cluster 2 showed weak transient increase. Mathematical modeling at single\u2010cell level revealed that the ATP production rate of cluster 1 was larger than that of cluster 2, and that both regulatory pathways of ATP production and consumption of cluster 1 were faster than those of cluster 2. Cluster 1 showed larger mitochondrial mass than cluster 2, suggesting that cluster 1 shows the similar property of slow muscle fibers, and cluster 2 shows the similar property of fast muscle fibers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Cluster 1 showed the stronger mitochondrial ATP increase by larger ATP production rate, but not smaller consumption. Cluster 1\u00a0might reflect the larger oxidative capacity of slow muscle fiber.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s40484-020-0211-8","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T12:03:22Z","timestamp":1595505802000},"page":"228-237","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Monitoring and mathematical modeling of mitochondrial ATP in myotubes at single\u2010cell level reveals two distinct population with different kinetics"],"prefix":"10.1002","volume":"8","author":[{"given":"Naoki","family":"Matsuda","sequence":"first","affiliation":[{"name":"<!--1--> Department of Biological Sciences Graduate School of Science University of Tokyo Tokyo 113\u20100033 Japan"}]},{"given":"Ken\u2010ichi","family":"Hironaka","sequence":"additional","affiliation":[{"name":"<!--1--> Department of Biological Sciences Graduate School of Science University of Tokyo Tokyo 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of Biological Sciences Nara Institute of Science and Technology Nara 630\u20100192 Japan"}]},{"given":"Haruki","family":"Inoue","sequence":"additional","affiliation":[{"name":"<!--5--> Department of Computational Biology and Medical Sciences Graduate School of Frontier Sciences University of Tokyo Tokyo 113\u20100033 Japan"}]},{"given":"Miki","family":"Eto","sequence":"additional","affiliation":[{"name":"<!--1--> Department of Biological Sciences Graduate School of Science University of Tokyo Tokyo 113\u20100033 Japan"}]},{"given":"Daisuke","family":"Hoshino","sequence":"additional","affiliation":[{"name":"<!--1--> Department of Biological Sciences Graduate School of Science University of Tokyo Tokyo 113\u20100033 Japan"},{"name":"<!--6--> Department of Engineering Science Graduate School of Informatics and Engineering University of Electro\u2010Communications Tokyo 182\u20108585 Japan"}]},{"given":"Yasuro","family":"Furuichi","sequence":"additional","affiliation":[{"name":"<!--7--> Department of Health Promotion Sciences Graduate School of Human Health Sciences Tokyo Metropolitan University Tokyo 192\u20100397 Japan"}]},{"given":"Yasuko","family":"Manabe","sequence":"additional","affiliation":[{"name":"<!--7--> Department of Health Promotion Sciences Graduate School of Human Health Sciences Tokyo Metropolitan University Tokyo 192\u20100397 Japan"}]},{"given":"Nobuharu L.","family":"Fujii","sequence":"additional","affiliation":[{"name":"<!--7--> Department of Health Promotion Sciences Graduate School of Human Health Sciences Tokyo Metropolitan University Tokyo 192\u20100397 Japan"}]},{"given":"Hiroyuki","family":"Noji","sequence":"additional","affiliation":[{"name":"<!--8--> Department of Applied Chemistry Graduate School of Engineering University of Tokyo Tokyo 113\u20108656 Japan"}]},{"given":"Hiromi","family":"Imamura","sequence":"additional","affiliation":[{"name":"<!--9--> Department of Functional Biology Graduate School of Biostudies Kyoto University Kyoto 606\u20108501 Japan"}]},{"given":"Shinya","family":"Kuroda","sequence":"additional","affiliation":[{"name":"<!--1--> Department of Biological Sciences Graduate School of Science University of Tokyo Tokyo 113\u20100033 Japan"},{"name":"<!--2--> Molecular Genetics Research Laboratory Graduate School of Science University of Tokyo Tokyo 113\u20100033 Japan"},{"name":"<!--10--> CREST Japan Science and Technology Corporation Tokyo 113\u20100033 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