Amino acid sensory complex proteins in mTORC1 and macroautophagy regulation.

Marcel Seibert, Nina Kurrle, Frank Schnütgen, Hubert Serve

Journal: Matrix biology : journal of the International Society for Matrix Biology 2022;100-101():65-83

PMID: 33429026

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Abstract

Autophagy is the highly conserved catabolic process, which enables the survival of a cell under unfavorable environmental conditions. In a constantly changing environment, cells must be capable of dynamically oscillating between anabolism and catabolism in order to maintain cellular homeostasis. In this context, the activity of the mechanistic Target Of Rapamycin Complex 1 (mTORC1) is of major importance. As a central signaling node, it directly controls the process of macroautophagy and thus cellular metabolism. Thereby, the control of mTORC1 is equally crucial as the regulation of cellular homeostasis itself, whereby particular importance is attributed to amino acid sensory proteins. In this review, we describe the recent findings of macroautophagy and mTORC1 regulation by upstream amino acid stimuli in different subcellular localizations. We highlight in detail which proteins of the sensor complexes play a specific role in this regulation and point out additional non-canonical functions, e.g. in the regulation of macroautophagy, which have received little attention so far.

Address: Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe-University Frankfurt, 60590 Frankfurt/Main, Germany; German Cancer Consortium (DKTK), partner site Frankfurt/Mainz, and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe-University Frankfurt, 60590 Frankfurt/Main, Germany; German Cancer Consortium (DKTK), partner site Frankfurt/Mainz, and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Frankfurt Cancer Institute, Goethe-University Frankfurt, 60596 Frankfurt/Main, Germany. Electronic address: [email protected].; Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe-University Frankfurt, 60590 Frankfurt/Main, Germany; German Cancer Consortium (DKTK), partner site Frankfurt/Mainz, and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Frankfurt Cancer Institute, Goethe-University Frankfurt, 60596 Frankfurt/Main, Germany.; Department of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe-University Frankfurt, 60590 Frankfurt/Main, Germany; German Cancer Consortium (DKTK), partner site Frankfurt/Mainz, and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Frankfurt Cancer Institute, Goethe-University Frankfurt, 60596 Frankfurt/Main, Germany. Electronic address: [email protected].

DOI: 10.1016/j.matbio.2021.01.001

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MeSH Terms: Amino Acids, Autophagy, Macroautophagy, Mechanistic Target of Rapamycin Complex 1, Signal Transduction