Abstract
Autophagy is a ubiquitous and conserved process in eukaryotic cells from yeasts to mammals. It also appears to play vital roles in plant pathogenic fungi, impacting growth, morphology, development, and pathogenicity. In this chapter, we have introduced a new concept to delineate the role of autophagy in homeostasis of plant pathogenic fungi and in their interaction with host cells, in breach of host barrier, and in the mechanisms of plant fungal infection.
Keywords
- plant pathogenic fungi
- autophagy
- selective autophagy
- process and function
- molecular mechanism
1. Introduction of plant pathogenic fungi
Filamentous fungi play important roles in health care, agriculture, and bioprocessing. There are thousands of species of plant pathogenic fungi that collectively are responsible for 70% of all known plant diseases. An improved understanding of the molecular mechanisms of plant fungal pathogenesis will ultimately lead to better control of plant fungal diseases. However, until recently, the complexity of fungal pathogen-plant host interactions made for slow progress in understanding both the mechanisms of plant host resistance and fungal pathogenesis. Over the last 40 years, the development and application of productive approaches based on genetics and molecular biology has led to the cloning and analysis of many plant resistance genes and fungal pathogenesis determinants to reveal a plethora of fungus-plant molecular interactions [1–3]. Diverse plant organs present different obstacles to infection by potential fungal pathogens, and therefore successful pathogens have evolved specific strategies, especially infection structures, that are able to break through host plant roots, stems, leaves, flowers, or other special tissues. These infection structures are usually modified hyphae specialized for the invasion of the target host plant tissue(s).
The typical life cycle of plant pathogenic fungi includes an asexual and a sexual stage. In the asexual stage, pathogens often repeatedly produce many asexual spores during the crop growing season; these play important roles in the spread of plant disease. The asexual spores germinate into filamentous hyphae, which can differentiate into a series of complex infection structures such as infection cushions, haustoria, appressoria, penetration pegs, and others [4]. This stage plays an important role in the spread of plant disease. When the vegetative growth stage reaches a certain period of time, fungi begin to enter the sexual stage to form various sexual spores, which are the initial sources of infection during the next disease cycle, in addition to giving rise to offspring and aiding pathogenic fungi in adverse environments. In favor of pathogens undergoing successful sporulation and infection, autophagy plays important roles in nutrient homeostasis. However, studies examining the role of autophagy are still not advanced in plant pathogenic fungi. With the publication of the genome sequence of
The rice blast fungus,
The ascomycete
In addition, the genetic models
2. Autophagy: functional roles in eukaryotes
Autophagy is an intracellular degradation system that is highly conserved in eukaryotic cells, which degrade proteins and organelles in the vacuole/lysosome. Studies examining the functions of autophagy have increased significantly in the last decade. Autophagy has a wide variety of functions in eukaryotic cells and intensive studies have shown that autophagy is not only involved in nutrient recycling but also in other cellular processes such as cellular differentiation, growth, and pathogenicity [13–18].
Autophagy is a general term for the degradation of cytoplasmic components within lysosomes. This process is quite distinct from general endocytosis-mediated lysosomal degradation of extracellular and plasma membrane proteins [19]. There are three types of autophagy that are classified based on the different ways in which a substrate in the cytoplasm can be transferred into the vacuole/lysosome: macroautophagy, microautophagy, and
c haperone-m ediateda utophagy (CMA). In general, we often consider the term “autophagy” to refer to macroautophagy. In recent years, given the selectivity of substrates for degradation, autophagy has been divided into two types: selective autophagy and nonselective autophagy [16–18, 20]. The unique organelle, called the autophagosome, mediates autophagy but where and how autophagosomes emerge has been a major question. In yeast, more than 38 Atg (autophagy-related) proteins have been identified, and most of them gather at a site that can be identified by fluorescence microscopy as a punctate spot very close to the vacuolar membrane. As autophagosomes are generated from this site, it is called the “p rea utophagosomals tructure” (PAS) [21, 22]. However, the structure of the PAS has not been characterized until now.
2.1. Autophagy/autolysosomal events
In mammals, the regulation of autophagy is highly complicated. Limited numbers of studies examining autophagy in filamentous fungi have extended the knowledge gleaned from
2.2. The induction and inhibition of autophagy
Like yeast or mammals, fungal autophagy is typically induced by nutrition (e.g., carbon and nitrogen) starvation [24]. Conversely, autophagy is inhibited by the mammalian target of rapamycin (mTOR), a central cell growth regulator that is connected with growth factor and nutrient sensing. It has been demonstrated that the molecular mechanism is regulated by the mammalian autophagy-initiating kinase Ulk1, a homolog of yeast Atg1 [25]. Under nutrient-rich conditions, TOR kinase is activated and phosphorylates Atg13. Phosphorylated Atg13 does not possess sufficient affinity for the Atg1 kinase and cannot form a complex with Atg1. Thus, the process of autophagy is inhibited [26, 27].
Rapamycin is an inducer of autophagy as inhibition of mTOR mimics cellular starvation by blocking signals required for cell growth and proliferation. Fungi can also be induced by treatment with rapamycin, often with concentrations between 200 and 500 ng/ml in fungal culture [23, 24, 28, 29].
2.3. Autophagy in nutrient recycling
Under nutrient-limited conditions, autophagy can serve as a nutrient recycling pathway to support cell survival [30]. This role was demonstrated in the autophagy-deficient
2.4. Autophagy in cellular degradation
Filamentous fungi have no lysosomes, like mammals, but the vacuoles play a similar role as degradative organelles. Hyphal vacuolation has been shown to increase rapidly in nutrient-starved
2.5. Autophagy in cellular differentiation
In eukaryotic cells, autophagy is involved in cellular differentiation and development [14]. In plant pathogenic fungi, blocked autophagy impacts the phenotypes and morphologies of fungi. In the
3. Macroautophagy-related genes studied in plant pathogenic fungi
Macroautophagy is the most widely studied type of autophagy. Many
3.1. The Atg1 kinase complex
In
Upon starvation induction, Atg13 is rapidly dephosphorylated and subsequently activates Atg1 kinase activity. Atg13 binds to the C-terminus of Atg1 and this interaction occurs in a constitutive manner [50]. Data from
3.2. Atg9-mediated vesicle transport
In yeast, Atg9 is a transmembrane protein consisting of six transmembrane domains with the amino and carboxyl termini exposed in the cytosol. Atg9 is positioned on the PAS and peripheral sites, shuttling and delivering membrane to form the phagophore. Atg1-Atg13 and Atg2-Atg18 facilitate Atg9-mediated vesicle transport from the PAS to peripheral sites [53], and the return of Atg9-mediated vesicle transport depends on Atg11, Atg23, and Atg27 [54, 55]. A new report indicates that Atg9 is a direct target of Atg1 kinase. Phosphorylated Atg9 is essential for the recruitment of Atg8 and Atg18 to the PAS and extension of the isolation membrane [56].
The functional characterization of Atg9 homologs in filamentous fungi has been documented. In
3.3. The two ubiquitin-like systems in autophagy
The process of autophagy involves two ubiquitin-like systems, the Atg12 and Atg8 conjugation systems. Both play key roles in bending and extension of the autophagosome membrane [45]. In the Atg12-Atg5-Atg16 ubiquitin-like system, Atg5 can directly bind the membrane, a process that is negatively regulated by Atg12 and positively regulated by Atg16 [57]. Identification of the proteins associated with the autophagosome has been performed in filamentous fungi. Disruption of the gene
Atg8 is another ubiquitin-like protein associated with autophagosome formation throughout the autophagy process and is well conserved in most model organisms and higher eukaryotes. It is associated with the autophagosome membrane and has been used as a marker for autophagy [60]. The amount of Atg8 can regulate the volume of autophagosomes by controlling phagophore expansion [61, 62]. The Atg12-Atg5-Atg16 complex acts like an E3 ligase, catalyzing Atg8 to phosphatidylethanolamine (PE) on the membrane [57].
Deletion of the
The Atg12 and Atg8, two ubiquitin-like conjugating systems, share the same E1-like activating enzyme, Atg7, but have different E2-like conjugating enzymes: Atg10 and Atg3, respectively [45]. In
3.4. The PI3K complex
Another protein complex required for autophagy in yeast is the phosphatidylinositol 3-kinase (PI3K) complex that involves Vps15, Vps34, Atg6, and Atg14 [45]. All of these proteins, with the exception of Atg14, are conserved in filamentous fungi. In
3.5. Membrane fusion
The membrane fusion of the autophagosome and vacuole requires many proteins. The autophagosome first docks with the surface of a vacuole, and then the outer membrane fuses with the vacuolar membrane. The proteins involved in this step are mostly those proteins which are implicated in membrane fusion, such as the SNARE family proteins and the homotypic fusion and vacuolar protein sorting (HOPS) tethering complex [70, 71]. Once inside the vacuolar lumen, the single-membrane vesicle turns into the autophagic body.
Many SNARE proteins have been characterized in plant pathogens especially in
3.6. Degradation of the autophagic body
The last step during autophagy is the degradation of the autophagic body in the vacuoles and recycling of cellular macromolecules to supply nutrient. Two autophagy-related proteins, Atg15 and Atg22, have been identified in yeast and are involved in this process [45]. Atg15 is a putative lipase involved in the lysis of CVT bodies, autophagic bodies, and incorporated peroxisomes in the vacuole [79]. Atg15 is well conserved in yeast and filamentous fungi, but it contains a distinct repeat motif at its C-terminus in front of the Ser/Thr-rich region [80]. In
4. Selective autophagy in plant pathogenic fungi
With the exception of bulk autophagy, which is nonselective, eukaryotic cells possess several types of selective autophagy to maintain homeostasis during stress. These processes include the CVT pathway (which is only found in
4.1. Pexophagy
Peroxisomes share enzymes involved in the β-oxidation of fatty acids and the production and degradation of H2O2 or other reactive oxygen species (ROS); thus, homeostasis in peroxisomes plays an important role in survival and development. Researchers have found that peroxisomes exhibit high variability under changing circumstances because their numbers can be rapidly increased when their functions are required but then can be quickly recycled when they are not essential to avoid wasting energy [84]. There are two biological processes that explain this phenomenon: the process of peroxisome growth and division and the specific degradation of peroxisomes by autophagy, known as pexophagy. Studies of methylotrophic yeasts have shown that two distinct, selective modes are exploited for pexophagy: macropexophagy and micropexophagy. It appears that high levels of ATP activate micropexophagy, while lower levels induce macropexophagy. Macropexophagy is initiated at a specific PAS (different from the CVT pathway); newly synthesized membrane wraps around and sequesters the peroxisomes one by one and then forms a double membrane pexophagosome, which is ultimately delivered to the vacuole. In contrast to macropexophagy, a cluster of peroxisomes is swallowed by vacuolar sequestering membranes (VSMs) in micropexophagy. Meanwhile, the micropexophagy-specific membrane apparatus (MIPA), which mediates fusion between the tips of the invagination vacuoles, extends from the PAS. Finally, membrane scission occurs on the inner side of the vacuolar membrane and the peroxisomes are cracked [85].
Among 38
In the cucumber anthracnose fungus
4.2. Mitophagy
Mitochondria are the sites of oxidative metabolism in eukaryotic organisms and are the places where the energy is released by the final oxidation of carbohydrates, fats, and amino acids. Reactive oxygen species are a side-product of the mitochondria. ROS release damages mitochondrial DNA and proteins and other cellular compartments, e.g., nuclear DNA. Thus, mitochondrial homeostasis is critical for organisms. Mitochondria degradation is mediated through a selective type of autophagy, called mitophagy. In
In
4.3. Reticulophagy and ribophagy
The ribosome is a cellular ribonucleoprotein particle that is primarily composed of RNA (rRNA) and proteins, and its only function is to catalyze amino acids for proteins according to the instructions imparted by the mRNA. Ribophagy involves degradation of the 60S ribosomal subunit and is regulated by both ubiquitination and deubiquitination. Some proteins are synthesized in the endoplasmic reticulum (ER) shortly after synthesis begins. The ER also modulates the modification and processing of protein folding and assembly and transport of nascent peptides. Like other selective autophagy pathways, reticulophagy and nucleophagy should be highly controlled. ERphagy is differentially induced, depending on the intensity and type of the ER stress [90]. This shows that the Ypt/Rab GTPase module, formed by the Trs85 containing the Ypt1, the Atg11 effector and the TRAPPIII GEF, functions in reticulophagy. With the exception of Ypt/Rab GTPases [91], macroreticulophagy also depends on Atgs and their cargos. In conclusion, Atg9-dependent ERphagy involved autophagy of the endoplasmic reticulum, Ypt1- and core Atg-dependent phagy mediate the organization of PAS, and Ypt51-dependent phagy mediates the delivery of autophagosomes to the vacuole [92].
Recently, researchers identified two Atg8-binding proteins in
4.4. Nucleophagy
The removal of damaged/nonessential/entire (in some circumstances) nuclei under stress is crucial for cell survival. Nucleophagy is the selective degradation of nuclear material by autophagy. It has two modes: macronucleophagy and micronucleophagy. Two processes (
Micronucleophagy has been studied in
In
5. Conclusions
In this report, we have introduced a new concept to delineate the role of autophagy in homeostasis of plant pathogenic fungi and in their interaction with host cells, breach of host barrier, and in the mechanisms of plant fungal infection. More knowledge of the diverse modes of autophagy is likely to help us understand the mechanisms of fungal pathogen-plant host interactions. In addition, pathogenic fungi are multicellular organisms that undergo constant polar growth that is completely different from yeast. Due to the differences between yeast and multicellular organisms, greater divergence has been revealed in terms of the CVT pathway, SNARE proteins, and selective autophagy, as mentioned in this chapter. It is necessary to create a new system to analyze autophagy in filamentous fungi. Furthermore, with the development of metabolomics and proteomics, studies of autophagy in plant pathogenic fungi can be combined with new technologies based on the molecular mechanisms of autophagy.
Acknowledgments
This study was supported by grants (no. 31371890 and no. 31370171) from the National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities.
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