Lysosomal cystine mobilization shapes the response of TORC1 and tissue growth to fasting.
Science
; 375(6582): eabc4203, 2022 02 18.
Article
em En
| MEDLINE
| ID: mdl-35175796
ABSTRACT
Adaptation to nutrient scarcity involves an orchestrated response of metabolic and signaling pathways to maintain homeostasis. We find that in the fat body of fasting Drosophila, lysosomal export of cystine coordinates remobilization of internal nutrient stores with reactivation of the growth regulator target of rapamycin complex 1 (TORC1). Mechanistically, cystine was reduced to cysteine and metabolized to acetyl-coenzyme A (acetyl-CoA) by promoting CoA metabolism. In turn, acetyl-CoA retained carbons from alternative amino acids in the form of tricarboxylic acid cycle intermediates and restricted the availability of building blocks required for growth. This process limited TORC1 reactivation to maintain autophagy and allowed animals to cope with starvation periods. We propose that cysteine metabolism mediates a communication between lysosomes and mitochondria, highlighting how changes in diet divert the fate of an amino acid into a growth suppressive program.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Jejum
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Cistina
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Proteínas de Drosophila
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Drosophila melanogaster
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Alvo Mecanístico do Complexo 1 de Rapamicina
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Lisossomos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos