Growth, Differentiation and Sexuality

180 B.C.K. Lu
Although the cytological phenotype of autophagic
cell death (type II PCD) is distinct from
that of apoptotic cell death (type I PCD), the
two pathways are not mutually exclusive. In fact,
crosstalk in the same cell may occur (reviewed
in Bursch 2001; Cohen et al. 2002). Examples of
crosstalk is found in yeast defective of histone
chaperone where dead asf-1/cia-1 cells exhibit the
phenotype of apoptosis, together with autophagic
vesicles in the vacuole normally found in autophagy
(Yamaki et al. 2001). Moreover, a common
gene, Uth1, has been found in yeast that is required
for both apoptotic and autophagic pathways.
Uth1 is required for the late steps of Bax-induced
apoptosis, namely, mitochondrial lipid oxidation,
maintenance of plasma membrane integrity, and
accumulation of ROS (hydrogen peroxide). It
is also involved in a form of cell death that is
different from apoptosis, i.e., rapamycin-induced
cell death related to autophagy (Camougrand et al.
2003). For the latter, a Δuth1 mutant is resistant
to rapamycin, but only when cells are grown
on a non-fermentable carbon source (lactate)
under conditions in which mitochondria are
fully differentiated, indicating a mitochondria
connection.
Mitochondrial membrane permeabilization
(MMP) has been suggested as a major ‘checkpoint’
that determines whether apoptosis occurs in
higher eukaryotes. Induction of MMP at a low
level, not enough to trigger apoptosis, may trigger
mitochondria-specific autophagy. Here MMP may
provide a link for crosstalk between apoptotic and
autophagic cell-death pathways (Cohen et al. 2002).
It is interesting to note that down-regulation of the
antiapoptotic gene Bcl-2, byexpressionofaBcl-2
antisense message, causes massive autophagic cell
death in human leukemic HL60 cells (Saeki et al.
2000).
In C. cinereus (Coprinopsis cinerea) and allies,
mushrooms undergo deliquescence for spore dispersal
(Buller 1931; Moore 2003). After completion
of meiosis and spore formation, the basidia and the
neighboring cells exhibit a large number of multivesicular
bodies (mvb, Fig.9.2D);thisoccursbefore
stipe elongation and deliquescence. When a
C. cinereus fruiting body is pulverized in a buffer
solution, the crude extract contains enzymes that
can digest cell walls, proteins and all cellular components
(Lu, unpublished data). Although there is
no critical genetic study, it is quite possible that
deliquescence is a form of autophagic cell death in
which lysosomes are involved.
D. Autophagic Cell Death
and Tissue Remodeling
Autophagic cell death is involved in tissue remodeling,
organ morphogenesis, and cavity formation
in higher eukaryotes (see review in Bursch 2001).
Similar observation has been made in tissue remodeling
and gill development in the mushroom
of C. cinereus (Lu 1991). By light microscopy, at the
earliest stage of gill differentiation, the hymenium
appears solid, there are no gaps, and no cell
disintegration. Shortly after the gills are clearly
defined, the area of gill cavity appears to show
gaps, suggesting cellular disintegration, as if the
gills have been carved out (Lu 1991). By electron
microscopy, cells in the gill cavity area exhibit
prominent membrane blebbing, vacuolation,
multi-vesicular systems, and residual bodies in
the vacuoles, but no chromatin condensation
(Fig. 9.2E–F). These observations were criticized
as fixation artifacts (Moore 1996). If these were
fixation artifacts, one would expect such images
to be universally and randomly distributed in all
tissues. However, this is not the case; they occur
only in a destined area where cellular debris are
found, specifically in the gill cavity, and never in
the internal area of the gill domain (Fig. 9.2G).
Besides, the phenotypes of vacuolation in the
basidia of C. cinereus (Fig. 9.2F, as compared to
Fig. 9.2C) provide evidence that autophagic cell
deathmaybeinvolved.Imustadmitthattheseare
preliminary observations, and more studies are
needed to establish that ACD plays a key role in gill
morphogenesis in C. cinereus. Morphogenetic cell
death has also been observed in the development
of fungal fruiting bodies in Agaricus bisporus,
Coprinus domestica (Coprinellus domestica), and
other fungal species (Umar and van Griensven
1997, 1998).
VII. Meiotic Apoptosis
Meiosis is a vital link between the old and the new
generation in eukaryotic organisms (see Zickler,
Chap. 20, this volume). In fungi, having a haploid
life cycle, it starts with the meiotic DNA replication
that occurs before karyogamy (reviewed in
Lu 1996), during which two compatible nuclei of
a dikaryon fuse to form the only diploid nucleus in
the life cycle. Karyogamy is immediately followed
by meiotic division, in which events of homologous
chromosome pairing and genetic recombina-