gen sources, and the cAMP-dependent protein
kinase A complex, sensing glucose (Budovskaya et al. 2004; González and Hall 2017). In
the following nucleation phase, Atg1 complex
kinase activity results in the assembly of several
other Atg proteins and the phosphatidylinositol
kinase Vps34, which action recruits transmembrane protein Atg9-containing vesicles for the
transport to the phagophore assembly site (He
et al. 2008; Stjepanovic et al. 2017). Phagophore
expansion as the third phase includes two
ubiquitin-like conjugation systems (Atg8,
Atg12), which cooperate to transfer Atg8 to
the lipid phosphatidylethanolamine (PE). Conjugation of Atg8 to Atg8-PE requires a similar
mechanism of E1 activating, E2 conjugating,
and E3 ligase cascade as previously described
for other ubiquitin-like proteins (Liu et al.
2010b; see Sect. IV.A). After the fusion of the
outer phagosomal membrane with the vacuolar
membrane, vacuolar lipases such as Atg15
degrade the membrane of the released autophagic body. The permease Atg22 exports the degradation products into the cytoplasm for
recycling (Sugimoto et al. 2011; Ramya and
Rajasekharan 2016; Fig. 8.4).
Numerous fungal atg genes are essential for
growth or are required for development, pathogenicity, or the formation of secondary metabolites. An A. fumigatus atg1 deletion strain is
impaired in vegetative growth in the presence
of different nitrogen sources and produces less
asexual spores, but is not affected in pathogenicity (Richie et al. 2007; Richie and Askew
2008). A Penicillium chrysogenum atg1 mutant
strain shows increased penicillin production
due to an increased number of peroxisomes as
a result of impaired pexophagy (Bartoszewska
et al. 2011). Penicillin production takes place in
the cytosol and in peroxisomes (Meijer et al.
2010). The relocation of AcvA, the first enzyme
of the penicillin biosynthesis (d-(L-a-aminoadipyl)-L-cysteinyl-D-valine synthetase), from the
cytosol to the peroxisomes significantly
increased the penicillin production of A. nidulans by more than three-fold (Herr and Fischer
2014).
The genes for the ubiquitin-like Atg12 from
different yeasts are required for ascosporogenesis under nitrogen starvation, and the
corresponding gene of N. crassa supports efficient fruiting body formation (Mukaiyama
et al. 2010; Chinnici et al. 2014). In contrast, a
M. oryzae atg12-deficient strain can undergo
sexual development but is impaired in host
infection. Whereas the atg genes participating
in selective autophagy are dispensable, 22 nonselective M. oryzae atg genes are required for
pathogenicity (Kershaw and Talbot 2009). This
includes non-selective autophagy mutants,
which are unable to transport the cellular content from the conidiospore into the appressoria, impairing leaf penetration.
Defects in the UBL encoding gene atg8 as
well as in several other atg genes result in
impaired vegetative growth and a block in sexual development in S. macrospora (Nolting et al.
2009; Voigt and Po ¨ggeler 2013). Both autophagy UBLs are involved in aging of hyphae,
which change in their thickness from young
thin to old thick hyphae. Deletion of atg8 for
the UBL or of atg10 encoding the E2 conjugating enzyme for the Atg12 UBL shortened this
aging process in A. niger (Nitsche et al. 2013).
Aging of hyphae by autophagy might be due to
degradation of organelles in older hyphae,
which provides nutrients and building bricks
for tip growth (Shoji et al. 2010). The degradation by mitophagy of damaged mitochondria
increases presumably also fungal life span,
because it prevents the accumulation of ROS
or proapoptotic factors (Tyler and Johnson
2018).
Autophagy ensures survival during starvation, mediates nutrient supply for ascospore
formation, and transports hydrolytic enzymes
into the vacuoles in yeast. Autophagy protects
cells against toxic metabolites or macromolecules and damaged organelles by their degradation and export. In ascomycetes, autophagy is
required for development under starvation and
nutrient-rich conditions. Furthermore, pathogenicity and secondary metabolism rely on
autophagy.
8 Coordination of Fungal Secondary Metabolism and Development
195
kinase A complex, sensing glucose (Budovskaya et al. 2004; González and Hall 2017). In
the following nucleation phase, Atg1 complex
kinase activity results in the assembly of several
other Atg proteins and the phosphatidylinositol
kinase Vps34, which action recruits transmembrane protein Atg9-containing vesicles for the
transport to the phagophore assembly site (He
et al. 2008; Stjepanovic et al. 2017). Phagophore
expansion as the third phase includes two
ubiquitin-like conjugation systems (Atg8,
Atg12), which cooperate to transfer Atg8 to
the lipid phosphatidylethanolamine (PE). Conjugation of Atg8 to Atg8-PE requires a similar
mechanism of E1 activating, E2 conjugating,
and E3 ligase cascade as previously described
for other ubiquitin-like proteins (Liu et al.
2010b; see Sect. IV.A). After the fusion of the
outer phagosomal membrane with the vacuolar
membrane, vacuolar lipases such as Atg15
degrade the membrane of the released autophagic body. The permease Atg22 exports the degradation products into the cytoplasm for
recycling (Sugimoto et al. 2011; Ramya and
Rajasekharan 2016; Fig. 8.4).
Numerous fungal atg genes are essential for
growth or are required for development, pathogenicity, or the formation of secondary metabolites. An A. fumigatus atg1 deletion strain is
impaired in vegetative growth in the presence
of different nitrogen sources and produces less
asexual spores, but is not affected in pathogenicity (Richie et al. 2007; Richie and Askew
2008). A Penicillium chrysogenum atg1 mutant
strain shows increased penicillin production
due to an increased number of peroxisomes as
a result of impaired pexophagy (Bartoszewska
et al. 2011). Penicillin production takes place in
the cytosol and in peroxisomes (Meijer et al.
2010). The relocation of AcvA, the first enzyme
of the penicillin biosynthesis (d-(L-a-aminoadipyl)-L-cysteinyl-D-valine synthetase), from the
cytosol to the peroxisomes significantly
increased the penicillin production of A. nidulans by more than three-fold (Herr and Fischer
2014).
The genes for the ubiquitin-like Atg12 from
different yeasts are required for ascosporogenesis under nitrogen starvation, and the
corresponding gene of N. crassa supports efficient fruiting body formation (Mukaiyama
et al. 2010; Chinnici et al. 2014). In contrast, a
M. oryzae atg12-deficient strain can undergo
sexual development but is impaired in host
infection. Whereas the atg genes participating
in selective autophagy are dispensable, 22 nonselective M. oryzae atg genes are required for
pathogenicity (Kershaw and Talbot 2009). This
includes non-selective autophagy mutants,
which are unable to transport the cellular content from the conidiospore into the appressoria, impairing leaf penetration.
Defects in the UBL encoding gene atg8 as
well as in several other atg genes result in
impaired vegetative growth and a block in sexual development in S. macrospora (Nolting et al.
2009; Voigt and Po ¨ggeler 2013). Both autophagy UBLs are involved in aging of hyphae,
which change in their thickness from young
thin to old thick hyphae. Deletion of atg8 for
the UBL or of atg10 encoding the E2 conjugating enzyme for the Atg12 UBL shortened this
aging process in A. niger (Nitsche et al. 2013).
Aging of hyphae by autophagy might be due to
degradation of organelles in older hyphae,
which provides nutrients and building bricks
for tip growth (Shoji et al. 2010). The degradation by mitophagy of damaged mitochondria
increases presumably also fungal life span,
because it prevents the accumulation of ROS
or proapoptotic factors (Tyler and Johnson
2018).
Autophagy ensures survival during starvation, mediates nutrient supply for ascospore
formation, and transports hydrolytic enzymes
into the vacuoles in yeast. Autophagy protects
cells against toxic metabolites or macromolecules and damaged organelles by their degradation and export. In ascomycetes, autophagy is
required for development under starvation and
nutrient-rich conditions. Furthermore, pathogenicity and secondary metabolism rely on
autophagy.
8 Coordination of Fungal Secondary Metabolism and Development
195