Drosophila as a model system to study autophagy

Abstract

Originally identified as a response to starvation in yeast, autophagy is now understood to fulfill a variety of roles in higher eukaryotes, from the maintenance of cellular homeostasis to the cellular response to stress, starvation, and infection. Although genetics and biochemical studies in yeast have identified many components involved in autophagy, the findings that some of the essential components of the yeast pathway are missing in higher organisms underscore the need to study autophagy in more complex systems. This review focuses on the use of the fruitfly, Drosophila melanogaster as a model system for analysis of autophagy. Drosophila is an organism well-suited for genetic analysis and represents an intermediate between yeast and mammals with respect to conservation of the autophagy machinery. Furthermore, the complex biology and physiology of Drosophila presents an opportunity to model human diseases in a tissue specific and analogous context.

Fig. 1

Connecting the Insulin pathway to the Drosophila autophagy machinery. Both branches of the insulin pathway downstream of Akt regulate autophagy in Drosophila. Insulin signaling inhibits Tor, allowing for autophagic vesicle induction by a complex containing Atg1 and Atg13. The mechanism of autophagy induction by FOXO remains unknown, although it likely involves transcriptional regulation of autophagy-related (Atg) genes. Vesicle nucleation by the Class III PI3K/Vps34 complex is regulated, in part, by Tor/Atg1 activity. Elongation and completion of the autophagosome require the Atg8-PE and Atg12 ubiquitin-like conjugation systems. Many of the components of these complexes have been demonstrated to be active in Drosophila autophagy (colored boxes). However, the function of several conserved autophagy proteins (white boxes) in Drosophila remains undetermined