Autophagy in Nonmammalian Systems

Jahda H Hill, University of Maryland Biotechnology Institute, College Park, Maryland, USA
Eric H Baehrecke, University of Massachusetts Medical School, Worcester, Massachusetts, USA

Published online: September 2009

DOI: 10.1002/9780470015902.a0021582

Autophagy, or ‘self-eating’, is a catabolic process that enables lysosome-mediated degradation of cytoplasmic contents and recycling of macromolecules to be used in essential cellular processes. This process enables cells to survive during nutrient restriction, participates in cell death during development, and functions in clearance of protein aggregates and intracellular pathogens. Autophagy has been widely studied in yeast, Drosophila and Caenorhabditis elegans, and studies in these organisms have revealed regulation by multiple cellular pathways. These include cell growth regulators, such as the Class I PI3 kinase and target of rapamycin (TOR), as well as cell death regulators, including caspases. Defects in autophagy are associated with cancer, neurodegeneration and reduced lifespan. Genetic experiments in Drosophila and C. elegans have been critical in determining how impairment of autophagy functions in these diseases.

Key concepts

  • Several yeast screens in the 1990s revealed genes required for autophagy.
  • Over 30 atg genes have been shown to regulate autophagy.
  • Autophagy is induced in response to starvation and oxidative stress, enabling cells to recycle macromolecules and degrade damaged organelles.
  • Autophagy is required for steroid-triggered removal of larval tissues during Drosophila melanogaster development.
  • Autophagosomes can sequester intracellular pathogens, which evade the cell's phagocytic machinery, and traffic them to the lysosome for degradation.
  • Decreased autophagy leads to an inability to clear protein aggregates and mutant polyglutamine containing proteins from neurons in fly and worm neurodegeneration models.
  • Induction of autophagy in the adult fly brain by transgenic expression of ATG8 can extend lifespan, whereas knock down of atg7 or atg8 leads to increased neuronal cell death and reduced lifespan.

Keywords: autophagy; cell death; Drosophila; C. elegans; neurodegeneration

Figure 1. Regulation of autophagy. Class I PI3K negatively regulates autophagy via the kinase Tor. Inactivation of Tor by starvation or rapamycin treatment leads to induction of autophagy. Atg1 kinase activity is required for autophagy induction, and Atg1 binds to Atg13. Vps34, Vps15 and Atg6 regulate the formation of a double membrane phagophore around proteins and organelles to be degraded. Two ubiquitin-like conjugation pathways regulate the elongation of the autophagosome membrane. Atg8 is cleaved at the C-terminus by Atg4. Atg7 activates Atg12 and Atg8 in an adenosine triphosphate (ATP)-dependent manner. This is followed by covalent conjugation of Atg12 to Atg5 and Atg8 to the lipid phosphatidylinositol (PE). Atg5 binds noncovalently to Atg16, and Atg8-PE becomes anchored in the autophagosome membrane. The outer membrane of the autophagosome fuses with the lysosome, releasing the inner membrane and sequestered contents into the lysosome for degradation.
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Related Sub-Topics:

Intracellular and Extracellular Signalling | Cell Death and Cellular Senescence | Mechanisms of Cell Death, Senescence and Metabolism | Bacteria | Energetics and Catabolism
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Article Title: Autophagy in Nonmammalian Systems
 
How to Cite close
Hill, Jahda H, and Baehrecke, Eric H(Sep 2009) Autophagy in Nonmammalian Systems. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021582]