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or knockdown of either
Atg1
or
Atg18
severely delays midgut removal
(
Denton et al., 2009
). Additionally, overexpression of Atg1 in the larval
midgut is sufficient to induce autophagy and premature degradation
(
Denton, Chang, et al., 2012
). Surprisingly, caspases are active, but they
are not required for removal of the midgut (
Denton et al., 2009; Denton,
Shravage, Simin, Baehrecke, & Kumar, 2010
), indicating that there is a
complex relationship between autophagy and caspases in this tissue.
Autophagy and caspases have a complex relationship that may be context
dependent. During salivary gland degradation, the rise in ecdysone titer trig-
gers increased transcription of not only
Atg
genes but also the proapoptotic
genes,
rpr
and
hid
, caspases, the BCL-2 family member
buffy
,and
ark
,the
fly
Apaf-1
homologue (
Dorstyn, Colussi, Quinn, Richardson, & Kumar,
1999; Jiang, Baehrecke, & Thummel, 1997; Lee, Simon, Woodard, &
Baehrecke, 2002
). Caspase activation occurs in the glands, but expression
of the caspase inhibitor p35 only partially inhibits salivary gland degradation
(
Lee & Baehrecke, 2001
). Additionally,
ark
mutants have a partial salivary
gland degradation defect, but autophagy occurs normally, suggesting that
ark
may function downstream or parallel to autophagy in programmed cell
death (
Akdemir et al., 2006; Mills et al., 2006
). Significantly, inhibiting both
caspases and autophagy by expressing p35 in salivary glands of
Atg18
loss-of-
function mutants or with dominant negative Atg1 results in increased persis-
tence of the salivary glands (Berry & Baehrecke, 2007). These results suggest
that autophagy and caspases function in parallel during salivary gland cell
death. Many of the components of the apoptotic machinery are also
upregulated in dying midguts. Despite the presence of high levels of caspase
activity, p35 expression or genetic ablation of the canonical caspase activation
pathway has no effect on midgut degradation (
Denton et al., 2009
). This is in
contrast to what has been observed in salivary glands, and it would be inter-
esting to study what causes these distinct differences between how
programmed cell death is executed in these two tissues.
Although these
in vivo
studies indicate a role for autophagy in
programmed cell death, the mechanistic differences that determine whether
autophagy will support cell survival or cell death are not clear. Recently,
Draper (Drpr), the
Drosophila
homologue of
Caenorhabditis elegans
engulf-
ment receptor CED-1, and other components of the engulfment pathway
were shown to be required for induction of autophagy during cell death
(
McPhee, Logan, Freeman, & Baehrecke, 2010
). Null mutations in
drpr
and salivary gland-specific knockdown of
drpr
prevent induction of
autophagy and cause persistent salivary glands. Expression of Atg1 in
drpr
