Biology Reference
In-Depth Information
1. INTRODUCTION
All animals transition through several different stages during their
development. The first stage is embryonic development, followed by a ju-
venile growth phase, then sexual maturation, and finally reproductive adult-
hood. Some animals, such as mammals, exhibit few changes in their body
plan during development except for growth; human babies look like min-
iature adults. Other animals go through drastic changes, such as the frog,
starting its juvenile phase as a tadpole and developing into a frog. Progression
through the developmental stages requires the coordination of cell and tissue
growth, cell survival, and cell death. In the example of the frog, cell growth
allows the limbs to develop, and cell death causes the regression of the tad-
pole's tail. The balance of cell growth, survival, and death is critical to
maintaining homeostasis of the organism.
Autophagy is a catabolic process that functions at the crossroads of the
different cell fates. Autophagy is predominately associated with cell survival
in response to cellular stress; however, mounting evidence suggests that it
also plays a role in programmed cell death. Additionally, autophagy is reg-
ulated by the same pathways that control cell growth. Autophagy and the
pathways that regulate it have been studied extensively in the fruit fly
Drosophila melanogaster
. These studies have provided insights into the rela-
tionship between cell growth, cell death, and autophagy, but the questions
of how and why these signals are integrated remain poorly understood.
2. AUTOPHAGY
Autophagy is an important catabolic process in all eukaryotic cells.
There are three known types of autophagy: macroautophagy, micro-
autophagy, and chaperone-mediated autophagy (
Klionsky, 2005
). Mac-
roautophagy (hereafter referred to as autophagy) is the best characterized
of the three types, and it involves the sequestration of cytoplasmic compo-
nents and long-lived proteins into lysosomes for degradation. During
autophagy, an isolation membrane sequesters cytoplasmic material, and it
elongates to form a double-membrane vesicle, the autophagosome
(
Fig. 4.1
). The autophagosome traffics to the lysosomal compartment where
its outer membrane fuses with lysosomes and releases the inner cargo for
degradation. Lysosomal permeases then recycle the degradation products
back to the cytoplasm (
Mizushima & Komatsu, 2011
). Autophagy is an
