Autophagy response: manipulating the mTOR-controlled machinery by amino acids and pathogens

Claudio Marcelo Fader1, Milton Osmar Aguilera1, María Isabel Colombo2

  • 1Laboratorio de Biología Celular y Molecular, Instituto de Histología y Embriología (IHEM)-CONICET, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Casilla de Correo 56, Centro Universitario, Parque General San Martín, (5500), Mendoza, Argentina.

Amino Acids
|September 20, 2014
PubMed

Insights

Macroautophagy maintains cell balance through a lysosomal pathway, regulated by the mammalian target of rapamycin (mTOR) pathway. mTOR controls cell growth and autophagy, responding to stress signals like nutrient changes and pathogen invasion.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Macroautophagy is a fundamental cellular process for maintaining homeostasis.
  • It is triggered by various stress conditions, including nutrient deprivation and pathogen presence.
  • The mammalian target of rapamycin (mTOR) pathway is a key regulator of cellular processes, including autophagy, protein translation, and gene expression.

Purpose of the Study:

  • To review the critical role of mTOR as a master regulator of cell growth.
  • To explore the regulation of autophagy by mTOR, focusing on its role in cellular homeostasis.
  • To discuss the interplay between mTORC1, intracellular conditions, and the autophagy machinery.

Main Methods:

  • Literature review focusing on the mammalian target of rapamycin (mTOR) pathway.
  • Analysis of the role of intracellular amino acid availability and pH in autophagy regulation.
  • Examination of the localization of mTORC1 and autophagy components at the lysosomal surface.

Main Results:

  • mTOR acts as a central regulator integrating signals for cell growth and autophagy.
  • Intracellular amino acid levels and pH influence autophagic structure redistribution and mTORC1 activity.
  • Co-localization of mTORC1 and autophagy machinery at the lysosome provides a mechanism for metabolic control.

Conclusions:

  • mTOR is a pivotal regulator of cell growth and the autophagy pathway.
  • Lysosomal localization of mTORC1 and autophagy components is crucial for cellular metabolism and pathogen defense.
  • Understanding these mechanisms offers insights into cellular homeostasis and disease processes.

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