Advances in autophagy regulatory mechanisms

Laura E. Gallagher, Leon E. Williamson, Edmond Y. W. Chan

Research output: Contribution to journalReview article

Abstract

Autophagy plays a critical role in cell metabolism by degrading and recycling internal components when challenged with limited nutrients. This fundamental and conserved mechanism is based on a membrane trafficking pathway in which nascent autophagosomes engulf cytoplasmic cargo to form vesicles that transport their content to the lysosome for degradation. Based on this simple scheme, autophagy modulates cellular metabolism and cytoplasmic quality control to influence an unexpectedly wide range of normal mammalian physiology and pathophysiology. In this review, we summarise recent advancements in three broad areas of autophagy regulation. We discuss current models on how autophagosomes are initiated from endogenous membranes. We detail how the uncoordinated 51-like kinase (ULK) complex becomes activated downstream of mechanistic target of rapamycin complex 1 (MTORC1). Finally, we summarise the upstream signalling mechanisms that can sense amino acid availability leading to activation of MTORC1.

LanguageEnglish
Article number24
Number of pages30
JournalCells
Volume5
Issue number2
DOIs
Publication statusPublished - 13 May 2016

Fingerprint

Autophagy
Metabolism
Membranes
Physiology
Nutrients
Quality control
Recycling
Transport Vesicles
Phosphotransferases
Chemical activation
Availability
Lysosomes
Amino Acids
Degradation
Quality Control
Reference Values
Food
mechanistic target of rapamycin complex 1
Autophagosomes

Keywords

  • autophagy
  • amino acids
  • ULK
  • MTOR
  • autophagosome
  • isolation membrane
  • Beclin 1
  • YPS34
  • ATG14L

Cite this

Gallagher, L. E., Williamson, L. E., & Chan, E. Y. W. (2016). Advances in autophagy regulatory mechanisms. Cells, 5(2), [24]. https://doi.org/10.3390/cells5020024
Gallagher, Laura E. ; Williamson, Leon E. ; Chan, Edmond Y. W. / Advances in autophagy regulatory mechanisms. In: Cells. 2016 ; Vol. 5, No. 2.
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Gallagher, LE, Williamson, LE & Chan, EYW 2016, 'Advances in autophagy regulatory mechanisms' Cells, vol. 5, no. 2, 24. https://doi.org/10.3390/cells5020024

Advances in autophagy regulatory mechanisms. / Gallagher, Laura E.; Williamson, Leon E.; Chan, Edmond Y. W.

In: Cells, Vol. 5, No. 2, 24, 13.05.2016.

Research output: Contribution to journalReview article

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AU - Gallagher, Laura E.

AU - Williamson, Leon E.

AU - Chan, Edmond Y. W.

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AB - Autophagy plays a critical role in cell metabolism by degrading and recycling internal components when challenged with limited nutrients. This fundamental and conserved mechanism is based on a membrane trafficking pathway in which nascent autophagosomes engulf cytoplasmic cargo to form vesicles that transport their content to the lysosome for degradation. Based on this simple scheme, autophagy modulates cellular metabolism and cytoplasmic quality control to influence an unexpectedly wide range of normal mammalian physiology and pathophysiology. In this review, we summarise recent advancements in three broad areas of autophagy regulation. We discuss current models on how autophagosomes are initiated from endogenous membranes. We detail how the uncoordinated 51-like kinase (ULK) complex becomes activated downstream of mechanistic target of rapamycin complex 1 (MTORC1). Finally, we summarise the upstream signalling mechanisms that can sense amino acid availability leading to activation of MTORC1.

KW - autophagy

KW - amino acids

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KW - MTOR

KW - autophagosome

KW - isolation membrane

KW - Beclin 1

KW - YPS34

KW - ATG14L

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U2 - 10.3390/cells5020024

DO - 10.3390/cells5020024

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Gallagher LE, Williamson LE, Chan EYW. Advances in autophagy regulatory mechanisms. Cells. 2016 May 13;5(2). 24. https://doi.org/10.3390/cells5020024