iMPAQT reveals that adequate mitohormesis from TFAM overexpression leads to life extension in mice.

Autor:	Igami K; LSI Medience Corporation, Tokyo, Japan igami.ko@mu.medience.co.jp.; Kyushu Pro Search Limited Liability Partnership, Fukuoka, Japan.; Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan., Kittaka H; LSI Medience Corporation, Tokyo, Japan.; Kyushu Pro Search Limited Liability Partnership, Fukuoka, Japan., Yagi M; Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.; Clinical Chemistry, Division of Biochemical Science and Technology, Department of Health Sciences, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan., Gotoh K; Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.; Department of Laboratory Medicine, Tokai University School of Medicine, Kanagawa, Japan., Matsushima Y; Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.; Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Japan., Ide T; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Ikeda M; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Ueda S; Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan., Nitta SI; LSI Medience Corporation, Tokyo, Japan.; Kyushu Pro Search Limited Liability Partnership, Fukuoka, Japan., Hayakawa M; Kyushu Pro Search Limited Liability Partnership, Fukuoka, Japan., Nakayama KI; Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.; Anticancer Strategies Laboratory, TMDU Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Japan., Matsumoto M; Department of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan., Kang D; Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.; Kashiigaoka Rehabilitation Hospital, Fukuoka, Japan., Uchiumi T; Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan uchiumi.takeshi.008@m.kyushu-u.ac.jp.; Clinical Chemistry, Division of Biochemical Science and Technology, Department of Health Sciences, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2024 Apr 25; Vol. 7 (7). Date of Electronic Publication: 2024 Apr 25 (Print Publication: 2024).
DOI:	10.26508/lsa.202302498
Abstrakt:	Mitochondrial transcription factor A, TFAM, is essential for mitochondrial function. We examined the effects of overexpressing the TFAM gene in mice. Two types of transgenic mice were created: TFAM heterozygous ( TFAM Tg) and homozygous ( TFAM Tg/Tg) mice. TFAM Tg/Tg mice were smaller and leaner notably with longer lifespans. In skeletal muscle, TFAM overexpression changed gene and protein expression in mitochondrial respiratory chain complexes, with down-regulation in complexes 1, 3, and 4 and up-regulation in complexes 2 and 5. The iMPAQT analysis combined with metabolomics was able to clearly separate the metabolomic features of the three types of mice, with increased degradation of fatty acids and branched-chain amino acids and decreased glycolysis in homozygotes. Consistent with these observations, comprehensive gene expression analysis revealed signs of mitochondrial stress, with elevation of genes associated with the integrated and mitochondrial stress responses, including Atf4, Fgf21, and Gdf15. These found that mitohormesis develops and metabolic shifts in skeletal muscle occur as an adaptive strategy. (© 2024 Igami et al.)
Databáze:	MEDLINE
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