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Monitoring and mathematical modeling of mitochondrial ATP in myotubes at single-cell level reveals two distinct population with different kinetics

引用

Quantitative Biology 2020年第3期8卷 228-237页

作者： Naoki Matsuda Ken-ichi Hironaka Masashi Fujii Takumi Wada Katsuyuki Kunida Haruki Inoue Miki Eto Daisuke Hoshino yasuro furuichi Yasuko Manabe Nobuharu LFujii Hiroyuki Noji Hiromi Imamura Shinya Kuroda Department of Biological Sciences Graduate School of ScienceUniversity of TokyoTokyo 113-0033Japan Molecular Genetics Research Laboratory Graduate School of ScienceUniversity of TokyoTokyo 113-0033Japan Department of Mathematical and Life Sciences Graduate School of Integrated Sciences for LifeHiroshima UniversityHiroshima 739-8526Japan Laboratory of Computati onal Biology Graduate School of Biological SciencesNara Institute of Science and Tech no logyNara 630-0192Japan Department of Computational Biology and Medical Sciences Graduate School of Frontier SciencesUniversity of TokyoTokyo 113-0033Japan Department of Engineering Science Graduate School of Informatics and EngineeringUniversity of Electro-CommunicationsTokyo 182-8585Japan Department of Health Promotion Sciences Graduate School of Human Health SciencesTokyo Metropolitan UniversityTokyo 192-0397Japan Department of Applied Chemistry Graduate School of EngineeringUniversity of TokyoTokyo 113-8656Japan Department of Functional Biology Graduate School of BiostudiesKyoto UniversityKyoto 606-8501Japan CREST Japan Science and Technology CorporationTokyo 113-0033Japan

Backgrounds ATP is the major energy source for myotube contraction,and is quickly produced to compensate ATP consumption and to maintain sufficient ATP *** is consumed mainly in cytoplasm and produced in mitochondria during myotube *** understand the mechanism of ATP homeostasis during myotube contraction,it is essential to monitor mitochondrial ATP at single-cell level,and examine how ATP is produced and consumed in ***: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 *** constructed mathematical model of mitochondrial ATP at single-cell level,and analyzed kinetic parameters of ATP production and ***:We performed hierarchical clustering analysis of time course of mitochondrial ATP,which resulted in two *** 1 showed strong transient increase,whereas cluster 2 showed weak transient *** modeling at single-cell 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 *** 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 *** Cluster 1 showed the stronger mitochondrial ATP increase by larger ATP production rate,but not smaller *** 1 might reflect the larger oxidative capacity of slow muscle fiber.

关键词： mitocondrial ATP production ATP consumption single-cell analysis mathematical modeling

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