Biology Reference
In-Depth Information
Type II cell death is observed in a variety of organisms. The plant,
Arabidopsis
, requires type II cell death for the formation of tracheary ele-
ments (
Kwon et al., 2010
). Type II cell death has also been observed in sev-
eral tissues during mammalian development, including regression of the
corpus luteum and involution of mammary and prostate glands (
Clarke,
1990
). Type II cell death is best characterized in insects and has been ob-
served in several tissues during development, including dying flight muscles
of the Hawkmoth
Manduca sexta
(
Lockshin & Williams, 1965
), and
degrading salivary glands and midgut in
Drosophila
(
Lee & Baehrecke,
2001; Lee, Cooksey, & Baehrecke, 2002
). Although autophagosomes are
present in dying cells with type II morphology, the role of autophagy in cell
death remains controversial (Denton, Nicolson, et al., 2012;
Levine &Yuan,
2005
).
Studies of dying larval tissues during
Drosophila
metamorphosis have pro-
vided evidence for a role of autophagy in programmed cell death. As de-
scribed above, a peak in ecdysone titer triggers salivary gland degradation
during metamorphosis. Several
Atg
genes exhibit increased transcription
in salivary glands in response to the rise in ecdysone, including
Atg2
,
Atg3
,
Atg4
,
Atg5
,
Atg7
, and
Atg18
(
Gorski et al., 2003
; Lee et al., 2003).
Additionally, mutations in transcription factors downstream of the EcR in-
hibit transcription of
Atg
-related genes and prevent proper salivary gland cell
death (Lee et al., 2003), suggesting that ecdysone-induced autophagy pro-
motes cell death. It was not until recently though that the function of
autophagy in cell death was rigorously tested
in vivo
. Mutations in
Atg8
,
Atg18
,
Atg2
,or
Atg3
or decreased function of
Atg1
all result in incomplete
degradation of the larval salivary glands (Berry & Baehrecke, 2007). In ad-
dition, knockdown of
Atg3
,
Atg6
,
Atg7
,or
Atg12
specifically in the salivary
glands leads to incomplete gland destruction, suggesting that autophagy
functions in a tissue-autonomous manner in these dying cells (Berry &
Baehrecke, 2007). Moreover, misexpression of Atg1 in the salivary glands
induces autophagy and leads to premature gland degradation in a caspase-
independent manner (Berry & Baehrecke, 2007). This is in contrast to pre-
vious work which showed that overexpression of Atg1 in the fat body in-
duces cell death that depends on caspase function (
Scott et al., 2007
).
There is also mounting evidence for a role of autophagy during
programmed cell death of the larval midgut. Similar to salivary glands, larval
midgut destruction is triggered by a peak in ecdysone titer at the end of larval
development. The dying midguts have increased autophagosome formation,
and inhibition of autophagy by loss-of-function mutations in
Atg2
or
Atg18
