Biology Reference
In-Depth Information
mutants is sufficient to rescue the salivary gland degradation defect, indicat-
ing that Drpr functions upstream of autophagy. Surprisingly, clonal analysis
of degrading glands reveals that Draper functions in a cell-autonomous
manner, as there is only a reduction of autophagy in the
drpr
mutant
cells. Interestingly, knockdown of
drpr
in the fat body does not affect
starvation-induced autophagy, implicating
drpr
as the first known factor
to regulate autophagy's role in cell death but not cell survival (
McPhee
et al., 2010
). It would be interesting to further investigate how Drpr is reg-
ulated in salivary glands and why an engulfment receptor is functioning cell-
autonomously.
5. CONCLUSIONS
Organisms require a balance between cell survival and cell death to
maintain homeostasis, and although
in vivo
evidence supports a role for
autophagy in both cell survival and cell death, many fundamental questions
remain. Since autophagy is involved in both protecting and killing the cell, it
is important to determine the mechanisms that decide between these cell
fates. One possibility is that autophagy selectively depletes a cell survival fac-
tor or an essential organelle, which leads to cell death (
Abeliovich, 2007;
Nezis et al., 2010; Yu et al., 2006
). Another possibility is that there is a
threshold of autophagic flux that is crossed to promote cell death. Extended
growth factor withdrawal in apoptotic-resistant mouse cells leads to stress-
induced autophagy and eventual death by depletion of cellular resources
(
Lum et al., 2005
). Under more physiological conditions, degradation of
the
Drosophila
salivary glands and midgut is preceded by an increase in both
transcription of the
Atg
genes and autophagosome levels. Additionally, mis-
expression of Atg1 in several tissues promotes cell demise, supporting the
idea that excessive autophagy leads to cell death. However, excessive
autophagy might not always be enough to kill, and other death factors
may be required in addition to autophagy. Cell death induced by Atg1 mis-
expression in the fat body is caspase dependent. Further, salivary glands re-
quire caspases and autophagy, functioning in parallel, to fully degrade (
Berry
& Baehrecke, 2007
).
Autophagy has been shown to be both an alternative form of cell death
in nonphysiological conditions and a necessary component of cell death in
physiological contexts; however, why cells die by autophagy is not under-
stood. Apoptosis requires a phagocyte to engulf the dying cell, while auto-
phagic cell death has little or no phagocyte involvement. One possibility is
