Merck
  • Home
  • Search Results
  • Autophagy modulates amino acid signaling network in myotubes: differential effects on mTORC1 pathway and the integrated stress response.

Autophagy modulates amino acid signaling network in myotubes: differential effects on mTORC1 pathway and the integrated stress response.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2014-11-08)
Xinlei Yu, Yun Chau Long
ABSTRACT

Induction of autophagy and the integrated stress response is important for amino acid homeostasis. It remains unknown whether the autophagy coregulates both mechanistic target of rapamycin complex 1 (mTORC1) signaling and the integrated stress response. In mouse C2C12 myotubes, we found that amino acid limitation induced autophagy and that the subsequent release of amino acid is required to sustain mTORC1 signaling. Inhibition of autophagy by bafilomycin A1 or chloroquine treatment during amino acid scarcity abolished mTORC1 signaling, an effect that could be rescued by inhibiting protein synthesis or amino acid supplementation, respectively. Autophagy is required to sustain the balance of both essential and nonessential amino acids during amino acid starvation, and it has a predominant role over the ubiquitin-proteasome system in the regulation of mTORC1. Inhibition of autophagy was found to activate the integrated stress response, as well as eukaryotic initiation factor 2α (eIF2α) and its target genes independent of amino acid availability. Conversely, autophagy induction via mTOR inhibition is sufficient to reduce eIF2α phosphorylation. Thus, autophagy protects the eIF2α-mediated stress response independent of amino acid supply in cultured myotubes. Our results showed that autophagy uniquely modulates mTORC1 and the integrated stress response in an amino acid-dependent and -independent manner, respectively.

MATERIALS
Product Number
Brand
Product Description

Supelco
Fluoride ion solution for ISE, 0.1 M F-, analytical standard (for ion-selective electrodes)
Sigma-Aldrich
Sodium dodecyl sulfate solution, BioUltra, for molecular biology, 20% in H2O
Sigma-Aldrich
Sodium dodecyl sulfate solution, BioUltra, for molecular biology, 10% in H2O
Sigma-Aldrich
Sodium deoxycholate, BioXtra, ≥98.0% (dry matter, NT)
Sigma-Aldrich
Sodium fluoride, BioXtra, ≥99%
Sigma-Aldrich
Sodium fluoride, 99.99% trace metals basis
Sigma-Aldrich
Sodium deoxycholate, ≥97% (titration)
Sigma-Aldrich
Sodium fluoride, BioReagent, suitable for insect cell culture, ≥99%
Sigma-Aldrich
Sodium fluoride, anhydrous, powder, 99.99% trace metals basis
Sigma-Aldrich
Sodium fluoride 0.5 M solution
SAFC
Sodium deoxycholate
Supelco
Sodium Fluoride, Pharmaceutical Secondary Standard; Certified Reference Material
Sodium laurilsulfate, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Sodium fluoride, ReagentPlus®, ≥99%
Sigma-Aldrich
Sodium fluoride, puriss., meets analytical specification of Ph. Eur., BP, USP, 98.5-100.5% (calc. to the dried substance)
Sigma-Aldrich
Sodium fluoride, ACS reagent, ≥99%
Sigma-Aldrich
Sodium dodecyl sulfate, ≥98.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, tested according to NF, mixture of sodium alkyl sulfates consisting mainly of sodium dodecyl sulfate
Supelco
Sodium dodecyl sulfate, suitable for ion pair chromatography, LiChropur, ≥99.0%
Sigma-Aldrich
Sodium dodecyl sulfate, ≥90%
Sigma-Aldrich
Sodium dodecyl sulfate, BioUltra, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
Sodium orthovanadate, 99.98% trace metals basis
Sigma-Aldrich
Sodium pyrophosphate tetrabasic, ≥95%
Sigma-Aldrich
Bicinchoninic acid disodium salt hydrate, ≥98% (HPLC)
Sigma-Aldrich
Sodium dodecyl sulfate, ≥99.0% (GC), dust-free pellets
Sigma-Aldrich
Sodium dodecyl sulfate, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, 92.5-100.5% based on total alkyl sulfate content basis
Sigma-Aldrich
Sodium dodecyl sulfate, BioXtra, ≥99.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, ReagentPlus®, ≥98.5% (GC)
Sigma-Aldrich
Sodium fluoride solution