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Review
. 2008 Jul;4(5):557-62.
doi: 10.4161/auto.5782. Epub 2008 Feb 23.

Eating on the fly: function and regulation of autophagy during cell growth, survival and death in Drosophila

Thomas P Neufeld  1 , Eric H Baehrecke
Affiliations
Review

Eating on the fly: function and regulation of autophagy during cell growth, survival and death in Drosophila

Thomas P Neufeld et al. Autophagy. 2008 Jul.

Abstract

Significant progress has been made over recent years in defining the normal progression and regulation of autophagy, particularly in cultured mammalian cells and yeast model systems. However, apart from a few notable exceptions, our understanding of the physiological roles of autophagy has lagged behind these advances, and identification of components and features of autophagy unique to higher eukaryotes also remains a challenge. In this review we describe recent insights into the roles and control mechanisms of autophagy gained from in vivo studies in Drosophila. We focus on potential roles of autophagy in controlling cell growth and death, and describe how the regulation of autophagy has evolved to include metazoan-specific signaling pathways. We discuss genetic screening approaches that are being used to identify novel regulators and effectors of autophagy, and speculate about areas of research in this system likely to bear fruit in future studies.

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Figures

Figure 1
Figure 1
Autophagy and caspases function during type II autophagic cell death in Drosophila. Control salivary glands are completely destroyed by 24 hours after puparium formation. By contrast, inhibition of either caspases by expression of p35 or autophagy by expression of a dominant negative form of Atg1 results in partial degradation and incomplete clearance of salivary glands 24 hours after puparium formation. Expression of both p35 and dominant negative Atg1 results in intact salivary glands 24 hours after puparium formation. Data reformatted from Berry and Baehrecke.
Figure 2
Figure 2
Nutrient-dependent control of autophagy through the TOR pathway. Amino acids, glucose and other nutrients stimulate the protein kinase activity of TOR within the multi-component TOR complex 1 (TORC1) through poorly characterized sensing and signaling mechanisms. Starvation leads to loss of TORC1 activity, relieving the inhibition of the protein kinase Atg1 and leading to induction of autophagy. Overlayed on this basic scheme are number of positive and negative feedback mechanisms. Reduced TORC1 signaling leads to loss of S6K activity, resulting in both a direct reduction in autophagy and an upregulation of insulin signaling. In addition, autophagy is intrinsically self-limiting, as the nutrients generated by autophagy can serve to activate TORC1 signaling. Mutual inhibition of TOR and Atg1 results in a self-reinforcing feedback loop that may amplify changes in nutrient signals. In addition, Akt activity is stimulated by the rapamycin-insensitive TOR complex 2, but how this complex is regulated is poorly understood. Not shown in this diagram are TOR-independent effects of nutrients and Atg1-independent effects of TOR on autophagy.
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