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

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Abstract

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.

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Acknowledgments

We thank Francisco Marques (Newcastle University) for maintaining and providing primary human fibroblasts and Tom DiCesare (BARC, Whitehead Institute for Biomedical Research) for assistance with illustrations. B.C and V.I.K are supported by Biotechnology and Biological Sciences Research Council (BBSRC), UK. S.S. is thankful to the laboratory of Rudolf Jaenisch and Whitehead Institute for Biomedical Research for funding. V.I.K and S.S are Former Fellows at Hughes Hall, University of Cambridge, UK.

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The authors declare no conflict of interests.

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Authors and Affiliations

  1. Institute for Ageing and Health, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5PL, UK

    Bernadette Carroll & Viktor I. Korolchuk

  2. Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA, 02142, USA

    Sovan Sarkar

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  1. Bernadette Carroll
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  2. Viktor I. Korolchuk
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  3. Sovan Sarkar
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Correspondence to Viktor I. Korolchuk or Sovan Sarkar.

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Carroll, B., Korolchuk, V.I. & Sarkar, S. Amino acids and autophagy: cross-talk and co-operation to control cellular homeostasis. Amino Acids 47, 2065–2088 (2015). https://doi.org/10.1007/s00726-014-1775-2

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