Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Assunto da revista
País de afiliação
Intervalo de ano de publicação
1.
Cell Metab ; 30(6): 1040-1054.e7, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31523008

RESUMO

Mitochondrial dysfunction elicits stress responses that safeguard cellular homeostasis against metabolic insults. Mitochondrial integrated stress response (ISRmt) is a major response to mitochondrial (mt)DNA expression stress (mtDNA maintenance, translation defects), but the knowledge of dynamics or interdependence of components is lacking. We report that in mitochondrial myopathy, ISRmt progresses in temporal stages and development from early to chronic and is regulated by autocrine and endocrine effects of FGF21, a metabolic hormone with pleiotropic effects. Initial disease signs induce transcriptional ISRmt (ATF5, mitochondrial one-carbon cycle, FGF21, and GDF15). The local progression to 2nd metabolic ISRmt stage (ATF3, ATF4, glucose uptake, serine biosynthesis, and transsulfuration) is FGF21 dependent. Mitochondrial unfolded protein response marks the 3rd ISRmt stage of failing tissue. Systemically, FGF21 drives weight loss and glucose preference, and modifies metabolism and respiratory chain deficiency in a specific hippocampal brain region. Our evidence indicates that FGF21 is a local and systemic messenger of mtDNA stress in mice and humans with mitochondrial disease.


Assuntos
DNA Mitocondrial/metabolismo , Fatores de Crescimento de Fibroblastos/fisiologia , Mitocôndrias/metabolismo , Miopatias Mitocondriais/metabolismo , Estresse Fisiológico/fisiologia , Fatores Ativadores da Transcrição/metabolismo , Animais , Linhagem Celular , DNA Mitocondrial/genética , Escherichia coli , Feminino , Fatores de Crescimento de Fibroblastos/genética , Fator 15 de Diferenciação de Crescimento/metabolismo , Humanos , Masculino , Camundongos , Mitocôndrias/genética , Miopatias Mitocondriais/genética , Deleção de Sequência , Estresse Fisiológico/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA