ER-localized phosphatidylethanolamine synthase plays a conserved role in lipid droplet formation

Gok, Mehmet Oguz; Speer, Natalie Ortiz; Friedman, Jonathan R.

doi:10.1091/mbc.e21-11-0558-t

Cited by 13 publications

(12 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In M. oryzae, the involvement of PE biosynthesis in virulence may be through the regulation of the degradation and utilization of lipid droplets and glycogen during appressorium formation, which we showed are impaired in the Mopsd2 mutant (Fig. 1g, h) (Gok, et al, 2022). Deletion of MoFAS1, a gene encoding a fatty acid-degrading enzyme, results in defective melanin biosynthesis and impaired utilization of lipid droplets in M. oryzae, consistent with Mopsd2 (Sangappillai & Nadarajah, 2020).…”

Section: Discussionsupporting

confidence: 80%

Doxorubicin inhibits phosphatidylserine decarboxylase and confers broad-spectrum antifungal activity

Zhou

Zhao

Yang

et al. 2023

Preprint

View full text Add to dashboard Cite

As phospholipids of cell membranes, phosphatidylethanolamine (PE) and phosphatidylserine (PS) play crucial roles in glycerophospholipid metabolism. Broadly, some phospholipid biosynthesis enzymes serve as potential fungicide targets. Therefore, revealing the functions and mechanism of PE biosynthesis in plant pathogens would provide potential targets for crop disease control. We performed analyses including phenotypic characterizations, lipidomics, enzyme activity, site-directed mutagenesis, and chemical inhibition assays to study the function of PS decarboxylase-encoding gene MoPSD2 in rice blast fungus Magnaporthe oryzae. The Mopsd2 mutant was defective in development, lipid metabolism and plant infection. The PS level increased while PE decreased in Mopsd2, consistent with the enzyme activity. Furthermore, chemical doxorubicin inhibited the enzyme activity of MoPsd2 and showed antifungal activity against ten phytopathogenic fungi including M. oryzae and reduced disease severity of two crop diseases in the field. Three predicted doxorubicin-interacting residues are important for MoPsd2 functions. Our study demonstrates that MoPsd2 is involved in de novo PE biosynthesis and contributes to the development and plant infection of M. oryzae and that doxorubicin shows broad-spectrum antifungal activity as a fungicide candidate. The study also implicates that bacterium Streptomyces peucetius, which biosynthesizes doxorubicin, could be potentially used as an eco-friendly biocontrol agent.

show abstract

Section: Discussionsupporting

confidence: 80%

Doxorubicin inhibits phosphatidylserine decarboxylase and confers broad-spectrum antifungal activity

Zhou

Zhao

Yang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In M. oryzae , the involvement of PE biosynthesis in virulence may be through the regulation of the degradation and utilization of lipid droplets and glycogen during appressorium formation, which we showed are impaired in the Mopsd2 mutant (Fig. 1g,h) (Gok et al ., 2022). Deletion of MoFAS1 , a gene encoding a fatty acid‐degrading enzyme, results in defective melanin biosynthesis and impaired utilization of lipid droplets in M. oryzae , consistent with Mopsd2 (Sangappillai & Nadarajah, 2020).…”

Section: Discussionmentioning

confidence: 99%

Doxorubicin inhibits phosphatidylserine decarboxylase and confers broad‐spectrum antifungal activity

et al. 2023

View full text Add to dashboard Cite

As phospholipids of cell membranes, phosphatidylethanolamine (PE) and phosphatidylserine (PS) play crucial roles in glycerophospholipid metabolism. Broadly, some phospholipid biosynthesis enzymes serve as potential fungicide targets. Therefore, revealing the functions and mechanism of PE biosynthesis in plant pathogens would provide potential targets for crop disease control.We performed analyses including phenotypic characterizations, lipidomics, enzyme activity, site-directed mutagenesis, and chemical inhibition assays to study the function of PS decarboxylase-encoding gene MoPSD2 in rice blast fungus Magnaporthe oryzae.The Mopsd2 mutant was defective in development, lipid metabolism, and plant infection. The PS level increased while PE decreased in Mopsd2, consistent with the enzyme activity. Furthermore, chemical doxorubicin inhibited the enzyme activity of MoPsd2 and showed antifungal activity against 10 phytopathogenic fungi including M. oryzae and reduced disease severity of two crop diseases in the field. Three predicted doxorubicin-interacting residues are important for MoPsd2 functions.Our study demonstrates that MoPsd2 is involved in de novo PE biosynthesis and contributes to the development and plant infection of M. oryzae and that doxorubicin shows broad-spectrum antifungal activity as a fungicide candidate. The study also implicates that bacterium Streptomyces peucetius, which biosynthesizes doxorubicin, could be potentially used as an eco-friendly biocontrol agent.

show abstract

“…Two recent studies in yeast and mammals reported the presence of the PS decarboxylase enzyme PISD1 in ER subdomains where LD biogenesis occurs [99,100]. In human cells, Kumar et al revealed the existence of a second isoform of PISD that, instead of being localized to the mitochondrial inner membrane as the main isoform, is localized to the ER-derived LD.…”

Section: Mam and Mitochondrial Protein Interplay For Lipid Transfer A...mentioning

confidence: 99%

Emerging functions of the mitochondria–ER–lipid droplet three‐way junction in coordinating lipid transfer, metabolism, and storage in cells

Monteiro‐Cardoso,

Giordano

2024

FEBS Letters

View full text Add to dashboard Cite

Over the past two decades, we have witnessed a growing appreciation for the importance of membrane contact sites (CS) in facilitating direct communication between organelles. CS are tiny regions where the membranes of two organelles meet but do not fuse and allow the transfer of metabolites between organelles, playing crucial roles in the coordination of cellular metabolic activities. The significant advancements in imaging techniques and molecular and cell biology research have revealed that CS are more complex than what originally thought, and as they are extremely dynamic, they can remodel their shape, composition, and functions in accordance with metabolic and environmental changes and can occur between more than two organelles. Here, we describe how recent studies led to the identification of a three‐way mitochondria–ER–lipid droplet CS and discuss the emerging functions of these contacts in maintaining lipid storage, homeostasis, and balance. We also summarize the properties and functions of key protein components localized at the mitochondria–ER–lipid droplet interface, with a special focus on lipid transfer proteins. Understanding tripartite CS is essential for unraveling the complexities of inter‐organelle communication and cooperation within cells.

show abstract

ER-localized phosphatidylethanolamine synthase plays a conserved role in lipid droplet formation

Cited by 13 publications

References 48 publications

Doxorubicin inhibits phosphatidylserine decarboxylase and confers broad-spectrum antifungal activity

Doxorubicin inhibits phosphatidylserine decarboxylase and confers broad-spectrum antifungal activity

Doxorubicin inhibits phosphatidylserine decarboxylase and confers broad‐spectrum antifungal activity

Emerging functions of the mitochondria–ER–lipid droplet three‐way junction in coordinating lipid transfer, metabolism, and storage in cells

Contact Info

Product

Resources

About