Biology Reference
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mutant phenotypes, including reduced growth rate, smaller cell size, and
decreased survival (
Scott et al., 2004
). This suggests that under these conditions,
in contradiction to its role as a negative regulator of growth, autophagy is nec-
essary to promote cell survival and maintain growth.
The relationship between autophagy and growth signaling has also been
studied in the context of degrading tissues during
Drosophila
metamorphosis.
Growth arrest is required for the induction of autophagy in degrading sal-
ivary glands (Berry & Baehrecke, 2007). This growth arrest is regulated by
the class I PI3K pathway. Maintaining growth in the salivary glands through
expression of activated Ras, Akt, or the class I PI3K catalytic subunit Dp110,
inhibits autophagy and gland degradation. In addition, coexpression of a
dominant negative TOR with either Ras or Dp110 partially suppresses
the overgrowth phenotypes and the salivary gland degradation defects (Berry
& Baehrecke, 2007). These data suggest that cell growth regulators signal
through TOR to inhibit autophagy and prevent salivary gland degradation.
Further, overexpression of Atg1, which induces autophagy, suppresses the
Dp110 persistent salivary gland phenotype, while
Atg
loss-of-function mu-
tations cause persistent salivary glands (Berry & Baehrecke, 2007), indicating
that both growth arrest and autophagy are required for proper salivary gland
degradation.
A recent study has observed a similar relationship between growth arrest
and autophagy during midgut programmed cell death in
Drosophila
. In the
midgut, as in the salivary glands, growth arrest occurs before programmed
cell death induction (
Denton, Chang, et al., 2012
). When cell growth in
the midgut is maintained by expression of either activated Ras or Dp110,
autophagy is suppressed and midgut degradation is delayed (
Denton,
Chang, et al., 2012
). These results indicate a role for growth arrest in midgut
programmed cell death. In contrast, inhibition of growth by the expression
of PTEN or TSC1/TSC2, negative regulators of class I PI3K signaling, re-
sults in smaller midguts and premature autophagy induction. This growth
inhibition can be suppressed by knockdown of either
Atg1
or
Atg18
in a
PTEN or TSC1/TSC2 expressing background (
Denton, Chang, et al.,
2012
). Interestingly, knockdown of
Atg
genes alone in the midgut causes
persistent PI3K growth signaling and a significant delay in midgut degrada-
tion. These results suggest that in the midgut, growth and autophagy have a
reciprocal relationship as in the salivary glands; however, there is also a
feedback mechanism by which autophagy downregulates class I PI3K signal-
ing. The nature of this feedback mechanism is unknown and deserves future
investigation.
