mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to metabolic state.
Cell
; 152(4): 778-790, 2013 Feb 14.
Article
em En
| MEDLINE
| ID: mdl-23394946
ABSTRACT
Survival in the wild requires organismal adaptations to the availability of nutrients. Endosomes and lysosomes are key intracellular organelles that couple nutrition and metabolic status to cellular responses, but how they detect cytosolic ATP levels is not well understood. Here, we identify an endolysosomal ATP-sensitive Na(+) channel (lysoNa(ATP)). The channel is a complex formed by two-pore channels (TPC1 and TPC2), ion channels previously thought to be gated by nicotinic acid adenine dinucleotide phosphate (NAADP), and the mammalian target of rapamycin (mTOR). The channel complex detects nutrient status, becomes constitutively open upon nutrient removal and mTOR translocation off the lysosomal membrane, and controls the lysosome's membrane potential, pH stability, and amino acid homeostasis. Mutant mice lacking lysoNa(ATP) have much reduced exercise endurance after fasting. Thus, TPCs make up an ion channel family that couples the cell's metabolic state to endolysosomal function and are crucial for physical endurance during food restriction.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Canais de Cálcio
/
Canais de Sódio
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Trifosfato de Adenosina
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Serina-Treonina Quinases TOR
/
Lisossomos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article