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Essays Biochem. 2017 Dec 12;61(6):565-584. doi: 10.1042/EBC20170027. Print 2017 Dec 12.

mTORC1 as the main gateway to autophagy.

Author information

1
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE4 5PL, U.K.
2
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE4 5PL, U.K. viktor.korolchuk@ncl.ac.uk.

Abstract

Cells and organisms must coordinate their metabolic activity with changes in their environment to ensure their growth only when conditions are favourable. In order to maintain cellular homoeostasis, a tight regulation between the synthesis and degradation of cellular components is essential. At the epicentre of the cellular nutrient sensing is the mechanistic target of rapamycin complex 1 (mTORC1) which connects environmental cues, including nutrient and growth factor availability as well as stress, to metabolic processes in order to preserve cellular homoeostasis. Under nutrient-rich conditions mTORC1 promotes cell growth by stimulating biosynthetic pathways, including synthesis of proteins, lipids and nucleotides, and by inhibiting cellular catabolism through repression of the autophagic pathway. Its close signalling interplay with the energy sensor AMP-activated protein kinase (AMPK) dictates whether the cell actively favours anabolic or catabolic processes. Underlining the role of mTORC1 in the coordination of cellular metabolism, its deregulation is linked to numerous human diseases ranging from metabolic disorders to many cancers. Although mTORC1 can be modulated by a number of different inputs, amino acids represent primordial cues that cannot be compensated for by any other stimuli. The understanding of how amino acids signal to mTORC1 has increased considerably in the last years; however this area of research remains a hot topic in biomedical sciences. The current ideas and models proposed to explain the interrelationship between amino acid sensing, mTORC1 signalling and autophagy is the subject of the present review.

KEYWORDS:

amino acids; autophagy; lysosome; mTOR

PMID:
29233869
PMCID:
PMC5869864
DOI:
10.1042/EBC20170027
[Indexed for MEDLINE]
Free PMC Article

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