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1.
Atg26-mediated pexophagy and fungal phytopathogenicity 总被引:1,自引:0,他引:1
《Autophagy》2013,9(7):1041-1042
Colletotrichum orbiculare is a plant pathogenic fungus that causes disease on cucumber plants. A homologue of ATG26 (CoATG26) was identified as the gene involved in pathogenesis. The peroxisomes are degraded via pexophagy during formation of an infection structure called the appressorium of C. orbiculare. The Coatg26 mutant developed appressoria but exhibited a specific defect in the subsequent host invasion step. Importantly, the autophagic degradation of peroxisomes was significantly delayed in the appressoria of the Coatg26 mutant. Domain and localization analysis of CoAtg26 also demonstrated a strong correlation of functional pexophagy with pathogenicity. Furthermore, in contrast to the Coatg26 mutant, the Coatg8 mutant, defective in the entire autophagic pathway, could not form normal appressoria in the earlier steps of morphogenesis. These results indicate that CoAtg26-mediated pexophagy plays critical roles in host plant invasion. 相似文献
2.
Eukaryotic cells adapt their organelle composition and abundance according to environmental conditions. Analysis of the peroxisomal membrane protein Pex3 has revealed that this protein plays a crucial role in peroxisome maintenance as it is required for peroxisome formation, segregation and breakdown. Although its function in peroxisome formation and segregation was known to involve its recruitment to the peroxisomal membrane of factors specific for these processes, the role of Pex3 in peroxisome breakdown was unclear until our recent identification of Atg36 as a novel Saccharomyces cerevisiae Pex3-interacting protein. Atg36 is recruited to peroxisomes by Pex3 and is required specifically for pexophagy. Atg36 is distinct from Atg30, the pexophagy receptor identified in Pichia pastoris. Atg36 interacts with Atg11 in vivo, and to a lesser extent with Atg8. These latter proteins link autophagic cargo receptors to the core autophagy machinery. Like other autophagic cargo receptors, Atg36 is a suicide receptor and is broken down in the vacuole together with its cargo. Unlike other cargo receptors, the interaction between Atg36 and Atg8 does not seem to be direct. Our recent findings suggest that Atg36 is a novel pexophagy receptor that may target peroxisomes for degradation via a noncanonical mechanism. 相似文献
3.
《Autophagy》2013,9(11):1680-1681
Eukaryotic cells adapt their organelle composition and abundance according to environmental conditions. Analysis of the peroxisomal membrane protein Pex3 has revealed that this protein plays a crucial role in peroxisome maintenance as it is required for peroxisome formation, segregation and breakdown. Although its function in peroxisome formation and segregation was known to involve its recruitment to the peroxisomal membrane of factors specific for these processes, the role of Pex3 in peroxisome breakdown was unclear until our recent identification of Atg36 as a novel Saccharomyces cerevisiae Pex3-interacting protein. Atg36 is recruited to peroxisomes by Pex3 and is required specifically for pexophagy. Atg36 is distinct from Atg30, the pexophagy receptor identified in Pichia pastoris. Atg36 interacts with Atg11 in vivo, and to a lesser extent with Atg8. These latter proteins link autophagic cargo receptors to the core autophagy machinery. Like other autophagic cargo receptors, Atg36 is a suicide receptor and is broken down in the vacuole together with its cargo. Unlike other cargo receptors, the interaction between Atg36 and Atg8 does not seem to be direct. Our recent findings suggest that Atg36 is a novel pexophagy receptor that may target peroxisomes for degradation via a noncanonical mechanism. 相似文献
4.
《Autophagy》2013,9(1):17-20
Autophagy is a degradative pathway conserved among eukaryotes. It is a major route for degradation of long-lived proteins and entire organelles, such as peroxisomes. Atg26, a sterol glucosyltransferase, is specifically required for micro- and macropexophagy, but not for starvation-induced bulk autophagy in Pichia pastoris. Here we study the requirement of Saccharomyces cerevisiae Atg26 in the Cvt pathway, nonspecific autophagy and pexophagy. Our results show that the S. cerevisiae atg26? strain is not defective in prApe1 maturation, macroautophagy or peroxisome degradation, in contrast to the situation seen in Pichia pastoris. These studies highlight the importance of examining mutants in multiple organisms. 相似文献
5.
Sarah F. Burnett Jean-Claude Farré Taras Y. Nazarko Suresh Subramani 《The Journal of biological chemistry》2015,290(13):8623-8631
Pexophagy is a process that selectively degrades peroxisomes by autophagy. The Pichia pastoris pexophagy receptor Atg30 is recruited to peroxisomes under peroxisome proliferation conditions. During pexophagy, Atg30 undergoes phosphorylation, a prerequisite for its interactions with the autophagy scaffold protein Atg11 and the ubiquitin-like protein Atg8. Atg30 is subsequently shuttled to the vacuole along with the targeted peroxisome for degradation. Here, we defined the binding site for Atg30 on the peroxisomal membrane protein Pex3 and uncovered a role for Pex3 in the activation of Atg30 via phosphorylation and in the recruitment of Atg11 to the receptor protein complex. Pex3 is classically a docking protein for other proteins that affect peroxisome biogenesis, division, and segregation. We conclude that Pex3 has a role beyond simple docking of Atg30 and that its interaction with Atg30 regulates pexophagy in the yeast P. pastoris. 相似文献
6.
Iwata J Ezaki J Komatsu M Yokota S Ueno T Tanida I Chiba T Tanaka K Kominami E 《The Journal of biological chemistry》2006,281(7):4035-4041
Peroxisomes are degraded by autophagic machinery termed "pexophagy" in yeast; however, whether this is essential for peroxisome degradation in mammals remains unknown. Here we have shown that Atg7, an essential gene for autophagy, plays a pivotal role in the degradation of excess peroxisomes in mammals. Following induction of peroxisomes by a 2-week treatment with phthalate esters in control and Atg7-deficient livers, peroxisomal degradation was monitored within 1 week after discontinuation of phthalate esters. Although most of the excess peroxisomes in the control liver were selectively degraded within 1 week, this rapid removal was exclusively impaired in the mutant liver. Furthermore, morphological analysis revealed that surplus peroxisomes, but not mutant hepatocytes, were surrounded by autophagosomes in the control. Our results indicated that the autophagic machinery is essential for the selective clearance of excess peroxisomes in mammals. This is the first direct evidence for the contribution of autophagic machinery in peroxisomal degradation in mammals. 相似文献
7.
Taras Y. Nazarko Jean-Claude Farré Suresh Subramani 《Molecular biology of the cell》2009,20(17):3828-3839
Autophagy is a major pathway of intracellular degradation mediated by formation of autophagosomes. Recently, autophagy was implicated in the degradation of intracellular bacteria, whose size often exceeds the capacity of normal autophagosomes. However, the adaptations of the autophagic machinery for sequestration of large cargos were unknown. Here we developed a yeast model system to study the effect of cargo size on the requirement of autophagy-related (Atg) proteins. We controlled the size of peroxisomes before their turnover by pexophagy, the selective autophagy of peroxisomes, and found that peroxisome size determines the requirement of Atg11 and Atg26. Small peroxisomes can be degraded without these proteins. However, Atg26 becomes essential for degradation of medium peroxisomes. Additionally, the pexophagy-specific phagophore assembly site, organized by the dual interaction of Atg30 with functionally active Atg11 and Atg17, becomes essential for degradation of large peroxisomes. In contrast, Atg28 is partially required for all autophagy-related pathways independent of cargo size, suggesting it is a component of the core autophagic machinery. As a rule, the larger the cargo, the more cargo-specific Atg proteins become essential for its sequestration. 相似文献
8.
Autophagy is a degradative pathway conserved among eukaryotes. It is a major route for degradation of long-lived proteins and entire organelles, such as peroxisomes. Atg26, a sterol glucosyltransferase, is specifically required for micro- and macropexophagy, but not for starvation-induced bulk autophagy in Pichia pastoris. Here we study the requirement of Saccharomyces cerevisiae Atg26 in the Cvt pathway, nonspecific autophagy and pexophagy. Our results show that the S. cerevisiae atg26Delta strain is not defective in prApe1 maturation, macroautophagy or peroxisome degradation, in contrast to the situation seen in Pichia pastoris. These studies highlight the importance of examining mutants in multiple organisms. 相似文献
9.
Peroxisomes undergo rapid, selective autophagic degradation (pexophagy) when the metabolic pathways they contain are no longer required for cellular metabolism. Pex3 is central to the formation of peroxisomes and their segregation because it recruits factors specific for these functions. Here, we describe a novel Saccharomyces cerevisiae protein that interacts with Pex3 at the peroxisomal membrane. We name this protein Atg36 as its absence blocks pexophagy, and its overexpression induces pexophagy. We have isolated pex3 alleles blocked specifically in pexophagy that cannot recruit Atg36 to peroxisomes. Atg36 is recruited to mitochondria if Pex3 is redirected there, where it restores mitophagy in cells lacking the mitophagy receptor Atg32. Furthermore, Atg36 binds Atg8 and the adaptor Atg11 that links receptors for selective types of autophagy to the core autophagy machinery. Atg36 delivers peroxisomes to the preautophagosomal structure before being internalised into the vacuole with peroxisomes. We conclude that Pex3 recruits the pexophagy receptor Atg36. This reinforces the pivotal role played by Pex3 in coordinating the size of the peroxisome pool, and establishes its role in pexophagy in S. cerevisiae. 相似文献
10.
Peroxisomes are degraded by a selective type of autophagy known as pexophagy. Several different types of pexophagy have been reported in mammalian cells. However, the mechanisms underlying how peroxisomes are recognized by autophagy-related machinery remain elusive. PEX3 is a peroxisomal membrane protein (PMP) that functions in the import of PMPs into the peroxisomal membrane and has been shown to interact with pexophagic receptor proteins during pexophagy in yeast. Thus, PEX3 is important not only for peroxisome biogenesis, but also for peroxisome degradation. However, whether PEX3 is involved in the degradation of peroxisomes in mammalian cells is unclear. Here, we report that high levels of PEX3 expression induce pexophagy. In PEX3-loaded cells, peroxisomes are ubiquitinated, clustered, and degraded in lysosomes. Peroxisome targeting of PEX3 is essential for the initial step of this degradation pathway. The degradation of peroxisomes is inhibited by treatment with autophagy inhibitors or siRNA against NBR1, which encodes an autophagic receptor protein. These results indicate that ubiquitin- and NBR1-mediated pexophagy is induced by increased expression of PEX3 in mammalian cells. In addition, another autophagic receptor protein, SQSTM1/p62, is required only for the clustering of peroxisomes. Expression of a PEX3 mutant with substitution of all lysine and cysteine residues by arginine and alanine, respectively, also induces peroxisome ubiquitination and degradation, hence suggesting that ubiquitination of PEX3 is dispensable for pexophagy and an endogenous, unidentified peroxisomal protein is ubiquitinated on the peroxisomal membrane. 相似文献
11.
Turnover of damaged, dysfunctional, or excess organelles is critical to cellular homeostasis. We screened mutants disturbed in peroxisomal protein import, and found that a deficiency in the exportomer subunits Pex1, Pex6, and Pex15 results in enhanced turnover of peroxisomal membrane structures compared with other mutants. Strikingly, almost all peroxisomal membranes were associated with phagophore assembly sites in pex1Δ atg1Δ cells. Degradation depended on Atg11 and the pexophagy receptor Atg36, which mediates degradation of superfluous peroxisomes. Mutants of PEX1, PEX6, and PEX15 accumulate ubiquitinated receptors at the peroxisomal membrane. This accumulation has been suggested to trigger pexophagy in mammalian cells. We show by genetic analysis that preventing this accumulation does not abolish pexophagy in Saccharomyces cerevisiae. We find Atg36 is modified in pex1Δ cells even when Atg11 binding is prevented, suggesting Atg36 modification is an early event in the degradation of dysfunctional peroxisomal structures in pex1Δ cells via pexophagy. 相似文献
12.
The requirement of sterol glucoside for pexophagy in yeast is dependent on the species and nature of peroxisome inducers
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Nazarko TY Polupanov AS Manjithaya RR Subramani S Sibirny AA 《Molecular biology of the cell》2007,18(1):106-118
Sterol glucosyltransferase, Ugt51/Atg26, is essential for both micropexophagy and macropexophagy of methanol-induced peroxisomes in Pichia pastoris. However, the role of this protein in pexophagy in other yeast remained unclear. We show that oleate- and amine-induced peroxisomes in Yarrowia lipolytica are degraded by Atg26-independent macropexophagy. Surprisingly, Atg26 was also not essential for macropexophagy of oleate- and amine-induced peroxisomes in P. pastoris, suggesting that the function of sterol glucoside (SG) in pexophagy is both species and peroxisome inducer specific. However, the rates of degradation of oleate- and amine-induced peroxisomes in P. pastoris were reduced in the absence of SG, indicating that P. pastoris specifically uses sterol conversion by Atg26 to enhance selective degradation of peroxisomes. However, methanol-induced peroxisomes apparently have lost the redundant ability to be degraded without SG. We also show that the P. pastoris Vac8 armadillo repeat protein is not essential for macropexophagy of methanol-, oleate-, or amine-induced peroxisomes, which makes PpVac8 the first known protein required for the micropexophagy, but not for the macropexophagy, machinery. The uniqueness of Atg26 and Vac8 functions under different pexophagy conditions demonstrates that not only pexophagy inducers, such as glucose or ethanol, but also the inducers of peroxisomes, such as methanol, oleate, or primary amines, determine the requirements for subsequent pexophagy in yeast. 相似文献
13.
Sibirny AA 《Biochemistry. Biokhimii?a》2011,76(12):1279-1290
Autophagy is a process of recycling of the intracellular constituents using vacuoles (lysosomes). General autophagy occurs
due to involvement of highly conservative components found in all eukaryotes, from yeasts to higher plants and humans. Autophagy
also could be a selective process and be involved in regulation of the cellular number of organelles, including that of peroxisomes.
The process of specific autophagic peroxisome degradation is known as pexophagy. Yeasts appear to be convenient model for
studying molecular mechanisms of pexophagy, and most known ATG genes (from the term AuTophaGy) were identified in yeast studies. This review examines characteristics of general autophagy,
other types of autophagy as well as pexophagy, in particular, functions of Atg proteins in general autophagy and in macro-
and micropexophagy. Special attention is given to mechanisms of phagophore assembly, the role of phosphatidylinositol-3-phosphate
in pexophagy, the role of peroxines (proteins involved in peroxisome biogenesis) in pexophagy, as well as properties of Atg
proteins specifically involved in micropexophagy. 相似文献
14.
《Autophagy》2013,9(3):263-265
Recently, we showed that the requirement of sterol glucoside (SG) during pexophagy in yeasts is dependent on the species and the nature of peroxisome inducers. Atg26, the enzyme that converts sterol to SG, is essential for degradation of very large methanol-induced peroxisomes, but only partly required for degradation of smaller-sized oleate- and amine-induced peroxisomes in Pichia pastoris. Moreover, oleate- and amine-induced peroxisomes of another yeast, Yarrowia lipolytica, are degraded by an Atg26-independent mechanism. The same is true for degradation of oleate-induced peroxisomes in Saccharomyces cerevisiae. Here, we review our findings on the specificity of Atg26 function in pexophagy and extend our observations to the role of SG in the cytoplasm to vacuole targeting (Cvt) pathway and bulk autophagy. The results presented here and elsewhere indicate that Atg26 might increase the efficacy of all autophagy-related pathways in P. pastoris, but not in other yeasts. Recently, it was shown that P. pastoris Atg26 (PpAtg26) is required for elongation of the pre-autophagosomal structure (PAS) into the micropexophagic membrane apparatus (MIPA) during micropexophagy. Therefore, we speculate that SG might facilitate elongation of any double membrane from the PAS and this enhancer function of SG becomes essential when extremely large double membranes are formed.Addendum to:The Requirement of Sterol Glucoside for Pexophagy in Yeast Is Dependent on the Species and Nature of Peroxisome InducersT.Y. Nazarko, A.S. Polupanov, R.R. Manjithaya, S. Subramani and A.A. SibirnyMol Biol Cell 2007; 18:106-18 相似文献
15.
16.
《Autophagy》2013,9(5):835-845
Turnover of damaged, dysfunctional, or excess organelles is critical to cellular homeostasis. We screened mutants disturbed in peroxisomal protein import, and found that a deficiency in the exportomer subunits Pex1, Pex6, and Pex15 results in enhanced turnover of peroxisomal membrane structures compared with other mutants. Strikingly, almost all peroxisomal membranes were associated with phagophore assembly sites in pex1Δ atg1Δ cells. Degradation depended on Atg11 and the pexophagy receptor Atg36, which mediates degradation of superfluous peroxisomes. Mutants of PEX1, PEX6, and PEX15 accumulate ubiquitinated receptors at the peroxisomal membrane. This accumulation has been suggested to trigger pexophagy in mammalian cells. We show by genetic analysis that preventing this accumulation does not abolish pexophagy in Saccharomyces cerevisiae. We find Atg36 is modified in pex1Δ cells even when Atg11 binding is prevented, suggesting Atg36 modification is an early event in the degradation of dysfunctional peroxisomal structures in pex1Δ cells via pexophagy. 相似文献
17.
Autophagy targets cytoplasmic cargo to a lytic compartment for degradation. Autophagy-related (Atg) proteins, including the transmembrane protein Atg9, are involved in different steps of autophagy in yeast and mammalian cells. Functional classification of core Atg proteins in plants has not been clearly confirmed, partly because of the limited availability of reliable assays for monitoring autophagic flux. By using proUBQ10-GFP-ATG8a as an autophagic marker, we showed that autophagic flux is reduced but not completely compromised in Arabidopsis thaliana atg9 mutants. In contrast, we confirmed full inhibition of auto-phagic flux in atg7 and that the difference in autophagy was consistent with the differences in mutant phenotypes such as hypersensitivity to nutrient stress and selective autophagy. Autophagic flux is also reduced by an inhibitor of phosphatidylinositol kinase. Our data indicated that atg9 is phenotypically distinct from atg7 and atg2 in Arabidopsis, and we proposed that ATG9 and phosphatidylinositol kinase activity contribute to efficient autophagy in Arabidopsis. 相似文献
18.
Geetanjali Ganguli Kali Prasad Pattanaik Manaswini Jagadeb Avinash Sonawane 《Cellular microbiology》2020,22(9)
Mycobacterium tuberculosis survives inside the macrophages by employing several host immune evasion strategies. Here, we reported a novel mechanism in which M. tuberculosis acetyltransferase, encoded by Rv3034c, induces peroxisome homeostasis to regulate host oxidative stress levels to facilitate intracellular mycobacterial infection. Presence of M. tuberculosis Rv3034c induces the expression of peroxisome biogenesis and proliferation factors such as Pex3, Pex5, Pex19, Pex11b, Fis‐1 and DLP‐1; while depletion of Rv3034c decreased the expression of these molecules, thereby selective degradation of peroxisomes via pexophagy. Further studies revealed that M. tuberculosis Rv3034c inhibit induction of pexophagy mechanism by down‐regulating the expression of pexophagy associated proteins (p‐AMPKα, p‐ULK‐1, Atg5, Atg7, Beclin‐1, LC3‐II, TFEB and Keap‐1) and adaptor molecules (NBR1 and p62). Inhibition was found to be dependent on the phosphorylation of mTORC1 and activation of peroxisome proliferator activated receptor‐γ. In order to maintain intracellular homeostasis during oxidative stress, M. tuberculosis Rv3034c was found to induce degradation of dysfunctional and damaged peroxisomes through activation of Pex14 in infected macrophages. In conclusion, this is the first report which demonstrated that M. tuberculosis acetyltransferase regulate peroxisome homeostasis in response to intracellular redox levels to favour mycobacterial infection in macrophage. 相似文献
19.
Michitaro Shibata Kazusato Oikawa Kohki Yoshimoto Maki Kondo Shoji Mano Kenji Yamada Makoto Hayashi Wataru Sakamoto Yoshinori Ohsumi Mikio Nishimura 《The Plant cell》2013,25(12):4967-4983
The positioning of peroxisomes in a cell is a regulated process that is closely associated with their functions. Using this feature of the peroxisomal positioning as a criterion, we identified three Arabidopsis thaliana mutants (peroxisome unusual positioning1 [peup1], peup2, and peup4) that contain aggregated peroxisomes. We found that the PEUP1, PEUP2, and PEUP4 were identical to Autophagy-related2 (ATG2), ATG18a, and ATG7, respectively, which are involved in the autophagic system. The number of peroxisomes was increased and the peroxisomal proteins were highly accumulated in the peup1 mutant, suggesting that peroxisome degradation by autophagy (pexophagy) is deficient in the peup1 mutant. These aggregated peroxisomes contained high levels of inactive catalase and were more oxidative than those of the wild type, indicating that peroxisome aggregates comprise damaged peroxisomes. In addition, peroxisome aggregation was induced in wild-type plants by exogenous application of hydrogen peroxide. The cat2 mutant also contained peroxisome aggregates. These findings demonstrate that hydrogen peroxide as a result of catalase inactivation is the inducer of peroxisome aggregation. Furthermore, an autophagosome marker, ATG8, frequently colocalized with peroxisome aggregates, indicating that peroxisomes damaged by hydrogen peroxide are selectively degraded by autophagy in the wild type. Our data provide evidence that autophagy is crucial for quality control mechanisms for peroxisomes in Arabidopsis. 相似文献
20.
Taras Y. Nazarko 《Autophagy》2017,13(5):991-994
Peroxisome biogenesis disorders (PBDs) is a group of diseases caused by mutations in one of the peroxins, proteins responsible for biogenesis of the peroxisomes. In recent years, it became clear that many peroxins (e.g., PEX3 and PEX14) play additional roles in peroxisome homeostasis (such as promoting autophagic degradation of peroxisomes or pexophagy), which are often opposite to their originally established functions in peroxisome formation and maintenance. Even more interesting, the peroxins that make up the peroxisomal AAA ATPase complex (AAA-complex) in yeast (Pex1, Pex6 and Pex15) or mammals (PEX1, PEX6, PEX26) are responsible for the downregulation of pexophagy. Moreover, this might be even their primary role in human: to prevent pexophagy by removing from the peroxisomal membrane the ubiquitinated peroxisomal matrix protein import receptor, Ub-PEX5, which is also a signal for the Ub-binding pexophagy receptor, NBR1. Remarkably, the peroxisomes rescued from pexophagy by autophagic inhibitors in PEX1G843D (the most common PBD mutation) cells are able to import matrix proteins and improve their biochemical function suggesting that the AAA-complex per se is not essential for the protein import function in human. This paradigm-shifting discovery published in the current issue of Autophagy has raised hope for up to 65% of all PBD patients with various deficiencies in the AAA-complex. Recognizing PEX1, PEX6 and PEX26 as pexophagy suppressors will allow treating these patients with a new range of tools designed to target mammalian pexophagy. 相似文献