Biology Reference
In-Depth Information
Insulin
and
growth
Ecdysone
?
Autophagy
Figure 4.3 Relationship between ecdysone, autophagy, and insulin signaling and
growth. Ecdysone and insulin have opposing effects on autophagy; ecdysone induces
autophagy, and insulin inhibits autophagy through class I PI3K and TOR signaling.
Ecdysone and insulin also antagonize each other, suggesting that a balance between
these two hormones may be required to regulate autophagy. For example, increased
ecdysone would inhibit insulin signaling, releasing insulin's inhibition on autophagy
and further inducing autophagy. Whether autophagy itself regulates ecdysone and in-
sulin is unclear; however, in some contexts autophagy may be a negative regulator of
growth.
In contrast to mammalian systems,
Drosophila
has little genetic redundancy and
has single copies for most genes in the autophagic pathway and its regulatory
pathways. In addition, autophagy is induced in
Drosophila
tissues in response to
either nutrient starvation or the steroid hormone ecdysone (
Lee & Baehrecke,
2001; Lee, Cooksey, & Baehrecke, 2002; Rusten et al., 2004
).
4.1. Autophagy in growth and nutrient utilization
Autophagy is critical for proper nutrient utilization during
Drosophila
larval
development. In the fly, the major storage site for glycogen, lipids, and pro-
teins is the fat body, an organ that shares attributes with both mammalian
adipose tissue and liver. The fat body provides an excellent model for study-
ing the mechanisms that regulate autophagy. When larvae are deprived of
amino acids, autophagy is induced in the fat body, and this starvation-
induced autophagy is regulated by TOR signaling (
Scott, Schuldiner, &
Neufeld, 2004
). It has been shown that inactivation of TOR signaling either
by a
TOR
null mutant or by manipulating upstream regulators of TOR in-
duces autophagy in the fat body of feeding larvae. On the other hand, ac-
tivation of either TOR or class I PI3K suppresses starvation-induced
autophagy in the fat body (
Scott et al., 2004
). These results, taken together
