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with the result that constitutive expression of PI3K in the fat body causes
reduced viability during starvation (
Britton, Lockwood, Li, Cohen, &
Edgar, 2002
), suggest that proper regulation of the class I PI3K signaling
pathway is necessary for autophagy to promote survival during starvation.
In addition to being necessary for survival during starvation, autophagy
may have a critical role in lipid metabolism of the
Drosophila
fat body. In
mammalian cells, it has been shown that there is a connection between
autophagy and lipolysis as well as lipid storage. Singh et al. demonstrated that
triglycerides (TGs) and lipid droplet (LD) proteins were associated with both
autophagosomes and lysosomes. Moreover, inhibition of autophagy in
mouse liver cells led to increased TGs and LDs
in vitro
and
in vivo
, while in-
creased autophagy led to decreased TGs and LDs
in vitro
(
Singh et al., 2009
).
Their data suggests that lipid accumulation during autophagy inhibition is a
result of blocked lipolysis. By contrast, it has been shown that loss of either
Atg5
or
Atg7
in mouse adipocytes leads to reduced lipid accumulation and
impaired adipocyte differentiation (
Baerga, Zhang, Chen, Goldman, & Jin,
2009; Zhang et al., 2009
). Similar results were obtained in a recent study of
Drosophila
larval fat body.
Atg7
loss-of-function mutants had smaller LDs in
the fat body, indicating a lipid accumulation defect (Wang et al., 2012). One
possible explanation for the discrepancies between these studies is that
autophagy may affect lipid metabolism in a tissue-specific manner. It would
be interesting to further investigate the relationship between autophagy and
lipid metabolism and how it is regulated in different tissues.
Wang et al. (2012)
provided insight into the relationship between lipid
metabolism and autophagy. Members of the Rab small GTPase family have
been associated with LDs, and are known to participate in many cellular pro-
cesses, including endocytosis, exocytosis, autophagosome formation, lyso-
some formation, and signaling transduction (
Liu et al., 2007; Stenmark,
2009; Zehmer et al., 2009
). In a screen for Rab proteins that affect LD size,
Wang et al. found 18 Rab proteins that either increased or decreased LD size
(Wang et al., 2012). They focused onRab32 and showed that as well as having
smaller LDs,
Rab32
mutants have impaired autophagy in the fat body. Impor-
tantly, Rab32 localized on autophagosomes, but not LDs, suggesting that its
effect on LD size is due to regulation of autophagy rather than a direct effect
on LDs. Since different Rab proteins have different effects on LD size, inves-
tigating the remaining Rab proteins might shed some light on the regulation
of the relationship between autophagy and lipid metabolism.
Autophagy is also induced in the fat body and other tissues, including the
salivary glands and mid gut during development in response to rises in
