The crucial role of the regulatory mechanism of the Atg1/ULK1 complex in fungi

Cai, Yingying; Li, Lin; Zhu, Xue-Ming; Lu, Jianping; Liu, Xiaohong; Feng, Lin

doi:10.3389/fmicb.2022.1019543

Cited by 8 publications

(4 citation statements)

References 156 publications

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“…The autophagic process is initiated by nutrient starvation, followed by discontinuing TORC1 stimulation and subsequent activation of the Atg1 kinase complex [ 18 ]. The ULK1/2 complex, which is the mammalian ortholog of the yeast Atg1 complex, consists of ULK1/2, Atg13, focal adhesion kinase family-interacting protein of 200 kDa (FIP200), and Atg101 [ 19 ]. The kinase complex is one of the most upstream acting components of the autophagy machinery as it recruits downstream ATG proteins known as the Beclin1/ATG14/VPS15/VPS34 Class III PI3K complex to the autophagosome formation site and generates phosphatidylinositol 3-phosphate (PI3P) for the nucleation and formation of the autophagosomal phagophore [ 20 ].…”

Section: Forms and Working Mechanisms Of Autophagymentioning

confidence: 99%

Metabolic Role of Autophagy in the Pathogenesis and Development of NAFLD

Wirth

Koch

et al. 2023

Metabolites

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Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease, ranging from simple steatosis to hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Liver fibrosis, which portends a poor prognosis in NAFLD, is characterized by the excessive accumulation of extracellular matrix (ECM) proteins resulting from abnormal wound repair response and metabolic disorders. Various metabolic factors play crucial roles in the progression of NAFLD, including abnormal lipid, bile acid, and endotoxin metabolism, leading to chronic inflammation and hepatic stellate cell (HSC) activation. Autophagy is a conserved process within cells that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. Accumulating evidence has shown the importance of autophagy in NAFLD and its close relation to NAFLD progression. Thus, regulation of autophagy appears to be beneficial in treating NAFLD and could become an important therapeutic target.

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Section: Forms and Working Mechanisms Of Autophagymentioning

confidence: 99%

Metabolic Role of Autophagy in the Pathogenesis and Development of NAFLD

Wirth

Koch

et al. 2023

Metabolites

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“…As shown in Figure 7D , autophagy-related (Atg) upregulated at almost all steps. In particular, Atg1 , Atg13 , and Atg17 , which encode proteins that act as components of the Atg1 complex ( Cai et al., 2022 ), were upregulated. Similarly, Atg12 , Atg5 , and Atg16 , which encode proteins that act as components of the Atg12-Atg5-Atg16 complex ( Walczak and Martens, 2013 ) and are recruited to the pre-autophagosomal structure (PAS), were upregulated.…”

Section: Resultsmentioning

confidence: 99%

Isobavachalcone exhibits antifungal and antibiofilm effects against C. albicans by disrupting cell wall/membrane integrity and inducing apoptosis and autophagy

Qian,

Lu,

Gao

et al. 2024

Front. Cell. Infect. Microbiol.

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Isobavachalcone (IBC) is a natural flavonoid with multiple pharmacological properties. This study aimed to evaluate the efficacy of IBC against planktonic growth and biofilms of Candida albicans (C. albicans) and the mechanisms underlying its antifungal action. The cell membrane integrity, cell metabolic viability, and cell morphology of C. albicans treated with IBC were evaluated using CLSM and FESEM analyses. Crystal violet staining, CLSM, and FESEM were used to assess the inhibition of biofilm formation, as well as dispersal and killing effects of IBC on mature biofilms. RNA-seq combined with apoptosis and autophagy assays was used to examine the mechanisms underlying the antifungal action of IBC. IBC exhibited excellent antifungal activity with 8 μg/mL of MIC for C. albicans. IBC disrupted the cell membrane integrity, and inhibited biofilm formation. IBC dispersed mature biofilms and damaged biofilm cells of C. albicans at 32 μg/mL. Moreover, IBC induced apoptosis and autophagy-associated cell death of C. albicans. The RNA-seq analysis revealed upregulation or downregulation of key genes involved in cell wall synthesis (Wsc1 and Fks1), ergosterol biosynthesis (Erg3, and Erg11), apoptisis (Hsp90 and Aif1), as well as autophagy pathways (Atg8, Atg13, and Atg17), and so forth, in response to IBC, as evidenced by the experiment-based phenotypic analysis. These results suggest that IBC inhibits C. albicans growth by disrupting the cell wall/membrane, caused by the altered expression of genes associated with β-1,3-glucan and ergosterol biosynthesis. IBC induces apoptosis and autophagy-associated cell death by upregulating the expression of Hsp90, and altering autophagy-related genes involved in the formation of the Atg1 complex and the pre-autophagosomal structure. Together, our findings provide important insights into the potential multifunctional mechanism of action of IBC.

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“…10c and d ; e right). Clearly, formation of autophagic structures in Neurospora does not require ATG1 function, although Atg1 protein could have a downstream role in delivering autophagic organelles to vacuoles ( 34 , 35 ).…”

Section: Resultsmentioning

confidence: 99%

Morphodynamics of non-canonical autophagic structures in Neurospora crassa

Rivetta,

Allen,

Graham

et al. 2023

mSphere

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Autophagy is a major pathway for unspooling cytoplasmic constituents and recycling them. Here, we investigate autophagy in Neurospora crassa, a close ascomycete relative to the model yeast Saccharomyces cerevisiae . High-pressure-freeze and freeze-substitution techniques proved keys to preservation of the surprising autophagic structures observed in Neurospora by transmission electron microscopy and electron tomography. Depriving Neurospora of carbon triggers two parallel processes at the plasma membrane: formation of vacuoles, initially along the plasma membrane but stuffing 70%–80% of cytoplasmic volume after several hours. The vacuoles contain material left over from digested proteins, disrupted ribosomes or glycogen clumps, plus other discrete organelle-like objects. Also, they accumulate the canonical autophagy marker Atg8, appear to be lytic from the start, and probably grow from lysosomes. Formation of diverse phagophores and autophagosomes, multi-membrane organelles manufactured de novo by the plasma membrane—a feature so far unique to Neurospora . These autophagic structures can be observed attached either to the cell membrane, to the cell wall, or free in the cytoplasm, viz. as mature organelles after detachment from the cell membrane. Although phagophores are clearly observed in carbon-replete cells, their production increases with carbon starvation—and these, too, often appear lytic. ATG1 , the canonical initiator of phagophore formation in yeast, is not required for the formation of phagophores in Neurospora . This work provides clear structural and functional evidence that Neurospora ’s autophagic organelles differ from those observed by others in yeast. IMPORTANCE Neurospora is a quintessential tip-growing organism, which is well known for packaging and longitudinal transport of tip-building blocks. Thus far, however, little attention has been paid to the co-essential process of reclamation, that is—taking apart of upstream, older structural elements, otherwise known as “autophagy”. We are not yet prepared to set out the chemistry of that elaborate process, but its morphological start alone is worthy of attention. Carbon starvation triggers significant autophagic changes, beginning with prolific vacuolation along the plasma membrane, and eventual filling of 70% (or more) of cytoplasmic volume. Additionally, the Neurospora plasma membrane elaborates a variety of phagophores which themselves often look lytic. These have either dual enclosing membranes, like the familiar autophagosomes, can be doubled and have four wrapping membranes, or can be compounded with multiple membrane layers. These reclamation processes must be accommodated by the mechanism of tip growth.

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The crucial role of the regulatory mechanism of the Atg1/ULK1 complex in fungi

Cited by 8 publications

References 156 publications

Metabolic Role of Autophagy in the Pathogenesis and Development of NAFLD

Metabolic Role of Autophagy in the Pathogenesis and Development of NAFLD

Isobavachalcone exhibits antifungal and antibiofilm effects against C. albicans by disrupting cell wall/membrane integrity and inducing apoptosis and autophagy

Morphodynamics of non-canonical autophagic structures in Neurospora crassa

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