Regulation of Autophagy Machinery in Magnaporthe oryzae

Asif, Nida; Feng, Lin; Li, Lin; Zhu, Xue-Ming; Nawaz, Shahid

doi:10.3390/ijms23158366

Cited by 9 publications

(9 citation statements)

References 95 publications

(93 reference statements)

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“…TOR adjusts cellular functions based on nutrient availability: suppressing autophagy when nutrients are plentiful but triggering cellular degradation via autophagosomes when nutrients are scarce or TOR is inhibited by rapamycin. Studying its role in plant-infecting fungi may aid in the avoidance and healing of rice blast disease [16]. MoLst8 is a crucial component of the TOR complex, and our research has found that the absence of MoLST8 impairs TOR and autophagy.…”

Section: Discussionmentioning

confidence: 91%

MoLst8 regulates autophagy and lipid homeostasis inMagnaporthe oryzae

Cao,

Li,

Bao

et al. 2024

Preprint

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TOR, a widely conserved eukaryotic protein kinase, forms TORC1 and TORC2 to regulate diverse cell signaling. TORC1 controls protein synthesis, cell cycle, and autophagy, whereas TORC2 manages cell polarity, cytoskeleton, and membrane structure. Our previous research found that MoVast2, along with MoVast1, regulates TOR in rice blast fungus Magnaporthe oryzae, maintaining lipid and autophagy balance. Lst8, a key TOR complex component in yeast and mammalian cells. However, the precise role of MoLst8 in M. oryzae is still unclear. In this study, we obtained the DeltaMolst8 mutant through high-through gene knockout strategies. The results showed that loss of MoLST8 leading to a series of defects, such as growth and sporulation reduction, abnormal conidia, and loss of virulence. In addition, this mutant is highly sensitive to rapamycin, leading to growth arrest and autophagy impairment, indicated that MoLst8 positively regulates TORC1 for cellular growth, metabolism, and autophagy. Lipidomics analysis in the mutant revealed lipid metabolism dysregulation, sphingolipid reduction, disrupting membrane tension and homeostasis, suggested that TORC2 mediated lipid regulation is disordered in DeltaMolst8 mutant. Additionally, the study explored TOR-MAPK crosstalk, finding that the mutant shows heightened cell wall stress sensitivity but fails to restore integrity despite MAPK activation. These findings offer insights into MoLst8's role in fungal pathogenesis, contributing to an understanding of fungal biology and disease control strategies.

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Section: Discussionmentioning

confidence: 91%

MoLst8 regulates autophagy and lipid homeostasis inMagnaporthe oryzae

Cao,

Li,

Bao

et al. 2024

Preprint

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“…M. oryzae activates autophagy to counter host-imposed stress and facilitate infection ( 25 , 56 , 57 ). In yeast and mammalian cells, Atg1 is the conserved protein kinase that phosphorylates Atg9 to positively regulate autophagy ( 47 , 58 ).…”

Section: Discussionmentioning

confidence: 99%

“…Autophagosomes are double-membrane structures formed by the phagophores sequestering cytoplasmic elements ( 25 ). Their formation involves a highly regulated and continuous membrane fusion process, including the generation of autophagosomal membrane precursors and phagophore elongation ( 24 ).…”

Section: Introductionmentioning

confidence: 99%

MoMkk1 and MoAtg1 dichotomously regulating autophagy and pathogenicity through MoAtg9 phosphorylation in Magnaporthe oryzae

Kong,

Guo,

et al. 2024

mBio

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Autophagy is a central biodegradation pathway critical in eliminating intracellular cargo to maintain cellular homeostasis and improve stress resistance. At the same time, the key component of the mitogen-activated protein kinase cascade regulating cell wall integrity signaling MoMkk1 has an essential role in the autophagy of the rice blast fungus Magnaporthe oryzae . Still, the mechanism of how MoMkk1 regulates autophagy is unclear. Interestingly, we found that MoMkk1 regulates the autophagy protein MoAtg9 through phosphorylation. MoAtg9 is a transmembrane protein subjected to phosphorylation by autophagy-related protein kinase MoAtg1. Here, we provide evidence demonstrating that MoMkk1-dependent MoAtg9 phosphorylation is required for phospholipid translocation during isolation membrane stages of autophagosome formation, an autophagic process essential for the development and pathogenicity of the fungus. In contrast, MoAtg1-dependent phosphorylation of MoAtg9 negatively regulates this process, also impacting growth and pathogenicity. Our studies are the first to demonstrate that MoAtg9 is subject to MoMkk1 regulation through protein phosphorylation and that MoMkk1 and MoAtg1 dichotomously regulate autophagy to underlie the growth and pathogenicity of M. oryzae . IMPORTANCE Magnaporthe oryzae utilizes multiple signaling pathways to promote colonization of host plants. MoMkk1, a cell wall integrity signaling kinase, plays an essential role in autophagy governed by a highly conserved autophagy kinase MoAtg1-mediated pathway. How MoMkk1 regulates autophagy in coordination with MoAtg1 remains elusive. Here, we provide evidence that MoMkk1 phosphorylates MoAtg9 to positively regulate phospholipid translocation during the isolation membrane or smaller membrane structures stage of autophagosome formation. This is in contrast to the negative regulation of MoAtg9 by MoAtg1 for the same process. Intriguingly, MoMkk1-mediated MoAtg9 phosphorylation enhances the fungal infection of rice, whereas MoAtg1-dependant MoAtg9 phosphorylation significantly attenuates it. Taken together, we revealed a novel mechanism of autophagy and virulence regulation by demonstrating the dichotomous functions of MoMkk1 and MoAtg1 in the regulation of fungal autophagy and pathogenicity.

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“…Autophagy leads to the encapsulation of excess or damaged proteins or organelles in the cytoplasm into vesicles that fuse with lysosomes to form autolysosomes, which degrade their encapsulated contents [ 74 , 75 ]. This process is beneficial for cells to renew their organelles and prevent further impairment by damaged organelles.…”

Section: Molecular Mechanism Of If Alleviation Of Dn Progressionmentioning

confidence: 99%

Intermittent Fasting—A Healthy Dietary Pattern for Diabetic Nephropathy

Yang

Chen

et al. 2022

Nutrients

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Diabetic nephropathy (DN), a metabolic disease, is characterized by severe systemic metabolic disorders. A unique dietary pattern, such as intermittent fasting (IF) has shown promising protective effects on various metabolic diseases, such as diabetes and cardiovascular and nervous system diseases. However, its role in regulating kidney disease, especially in DN, is still being investigated. Here, we summarize the current research progress, highlighting the relationship between IF and the risk factors for the progression of DN, and discuss the potential mechanisms by which IF improves renal injury in DN. Finally, we propose IF as a potential strategy to prevent and delay DN progression. Abbreviation: DN: Diabetic nephropathy; IF: Intermittent fasting; CPT1A: Carnitine palmitoyltransferase 1A; L-FABP: Liver-type fatty acid-binding protein; STZ: Streptozotocin; LDL: Low-density lipoproteins; HIIT: High-intensity interval training; CKD: Chronic kidney disease; ACEI: Angiotensin-converting enzyme inhibitors; ARB: Angiotensin receptor blockers; MDA: Malondialdehyde; mtDNA: Mitochondrial DNA; UCP3: Uncoupling protein-3; MAM: Mitochondria-associated endoplasmic reticulum membrane; PBMCs: Peripheral blood mononuclear cells; ERK1/2: Extracellular signal-regulated kinase 1/2; DRP1: Dynamin-related protein 1; β-HB: β-Hydroxybutyrate; AcAc: Acetoacetate; GEO: Gene Expression Omnibus; NCBI: National Center for Biotechnology Information; mTORC1: Mechanistic target of rapamycin complex 1; HMGCS2: 3-Hydroxy-3-methylglutaryl-CoA synthase 2; GSK3β: Glycogen synthase kinase 3β; AKI: Acute kidney injury; CMA: Chaperone-mediated autophagy; FGF21: Fibroblast growth factor 21.

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Regulation of Autophagy Machinery in Magnaporthe oryzae

Cited by 9 publications

References 95 publications

MoLst8 regulates autophagy and lipid homeostasis inMagnaporthe oryzae

MoLst8 regulates autophagy and lipid homeostasis inMagnaporthe oryzae

MoMkk1 and MoAtg1 dichotomously regulating autophagy and pathogenicity through MoAtg9 phosphorylation in Magnaporthe oryzae

Intermittent Fasting—A Healthy Dietary Pattern for Diabetic Nephropathy

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