iMPAQT reveals that adequate mitohormesis from TFAM overexpression leads to life extension in mice.
Life Sci Alliance
; 7(7)2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38664021
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Camundongos Transgênicos
/
Proteínas de Grupo de Alta Mobilidade
/
Músculo Esquelético
/
Proteínas Mitocondriais
/
Proteínas de Ligação a DNA
/
Longevidade
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article