Amino acids and autophagy: Cross-talk and co-operation to control cellular homeostasis

Bernadette Carroll, Viktor I. Korolchuk*, Sovan Sarkar

*Corresponding author for this work

Research output: Contribution to journalReview article (Academic Journal)peer-review

52 Citations (Scopus)


Maintenance of amino acid homeostasis is important for healthy cellular function, metabolism and growth. Intracellular amino acid concentrations are dynamic; the high demand for protein synthesis must be met with constant dietary intake, followed by cellular influx, utilization and recycling of nutrients. Autophagy is a catabolic process via which superfluous or damaged proteins and organelles are delivered to the lysosome and degraded to release free amino acids into the cytoplasm. Furthermore, autophagy is specifically activated in response to amino acid starvation via two key signaling cascades: the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and the general control nonderepressible 2 (GCN2) pathways. These pathways are key regulators of the integration between anabolic (amino acid depleting) and catabolic (such as autophagy which is amino acid replenishing) processes to ensure intracellular amino acid homeostasis. Here, we discuss the key roles that amino acids, along with energy (ATP, glucose) and oxygen, are playing in cellular growth and proliferation. We further explore how sophisticated methods are employed by cells to sense intracellular amino acid concentrations, how amino acids can act as a switch to dictate the temporal and spatial activation of anabolic and catabolic processes and how autophagy contributes to the replenishment of free amino acids, all to ensure cell survival. Relevance of these molecular processes to cellular and organismal physiology and pathology is also discussed.

Original languageEnglish
Pages (from-to)2065-2088
Number of pages24
JournalAmino Acids
Issue number10
Publication statusPublished - 29 Oct 2015


  • Amino acid
  • Amino acid transporters
  • Arginine
  • Autophagy
  • eIF2
  • GCN2
  • Glutamine
  • Leucine
  • Lysosome
  • mTORC1

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