RT Journal Article
SR Electronic
T1 iMPAQT reveals that adequate mitohormesis from TFAM overexpression leads to life extension in mice
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202302498
DO 10.26508/lsa.202302498
VO 7
IS 7
A1 Igami, Ko
A1 Kittaka, Hiroki
A1 Yagi, Mikako
A1 Gotoh, Kazuhito
A1 Matsushima, Yuichi
A1 Ide, Tomomi
A1 Ikeda, Masataka
A1 Ueda, Saori
A1 Nitta, Shin-Ichiro
A1 Hayakawa, Manami
A1 Nakayama, Keiichi I.
A1 Matsumoto, Masaki
A1 Kang, Dongchon
A1 Uchiumi, Takeshi
YR 2024
UL http://www.life-science-alliance.org/content/7/7/e202302498.abstract
AB 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.Additional data are provided as Supplemental Data and Figures. The MS proteomics data have been deposited to the PanoramaWeb (https://panoramaweb.org) with the dataset Permanent Link: https://panoramaweb.org/GqfOgy.url.