Insights Into the Biogenesis and Emerging Functions of Lipid Droplets From Unbiased Molecular Profiling Approaches

Sánchez-Álvarez, Miguel; Pozo, Miguel Á. del; Bosch, Marta; Pol, Albert

doi:10.3389/fcell.2022.901321

Cited by 13 publications

(10 citation statements)

References 307 publications

(398 reference statements)

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“…Lipid droplets (LDs) are highly dynamic spherical organelles, which appear in the cytosol of most eukaryotic cell types [46] . Rapamycin treatment led to the accumulation of lipid droplets in various filamentous fungi [24] .…”

Section: Resultsmentioning

confidence: 99%

The TOR signaling pathway regulates vegetative development, aflatoxin biosynthesis, and pathogenicity inAspergillus flavus

Cao

Tumukunde

et al. 2023

Preprint

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The target of the rapamycin (TOR) signaling pathway is highly conserved and important in eukaryotes. It is involved in the regulation of various biological processes. However, systematic studies on this pathway in the genus Aspergillus have not been reported. Here, we identified and characterized nine genes encoding components of the TOR pathway in A. flavus, and investigated their biological, genetic and biochemical functions. The FK506-binding protein FKBP3 and its lysine succinylation are important for aflatoxin production and rapamycin resistance. The Tor kinase plays a central role in the global regulation of growth, spore production, aflatoxin biosynthesis and rapamycin stress. As a major downstream effector molecule of Tor kinase, the Sch9 kinase might regulate the calcium and osmotic stress, AFB1 synthesis of A. flavus by its S_TKc, S_TK_X domains and ATP binding site at K340. We also showed that Sch9 kinase might mediate crosstalk between the TOR and the HOG signaling pathways. TapA and TipA, the other downstream components of Tor kinase, play important roles in regulating mycelial growth and sclerotia formation in A. flavus. The member of the TapA-phosphatase complexes Sit4 and Ppg1 are important for hyphal development, sexual reproduction, sclerotia formation, AFB1 biosynthesis, activation of the CWI and TOR signaling pathways in A. flavus. In addition, the another phosphatase complex Nem1/Spo7 play critical role in vegetative growth, conidiation, aflatoxin and LD biogenesis. This study provide new insights into constructing the regulatory network of the TOR signaling pathway and revealing the molecular mechanism of the pathogenicity in A. flavus.

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Section: Resultsmentioning

confidence: 99%

The TOR signaling pathway regulates vegetative development, aflatoxin biosynthesis, and pathogenicity inAspergillus flavus

Cao

Tumukunde

et al. 2023

Preprint

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“…21,29 A major share of the knowledge behind this paradigm shift about the functions of LDs has been enabled by the use of systematic molecular profiling approaches, capable of revealing and describing non-intuitive systems-level relationships. 41…”

Section: Toxoplasma Gondimentioning

confidence: 99%

“…4,21,155 The use of novel systematic molecular profiling approaches, capable of revealing within the LD proteome non-intuitive systems-level relationships, decisively shifted the paradigm. 41 Although the presence of antiviral and antibacterial proteins on LDs was described long ago, 9,11 recent work from a number of different groups, including some highthroughput analyses, has illuminated the complex and bidirectional relationship between LDs and invaders. 12,42,79,149,156 The hypothesis that LDs are strategic chokepoints organizing a first defensive line of innate immunity has increasing support.…”

Section: Box 6 Interferons In Innate Immunitymentioning

confidence: 99%

“…The role of LDs in maintaining cellular homeostasis by functioning as generic stress buffers has been proposed 21,29 . A major share of the knowledge behind this paradigm shift about the functions of LDs has been enabled by the use of systematic molecular profiling approaches, capable of revealing and describing non‐intuitive systems‐level relationships 41 …”

Section: Lipid Droplets Manage the Nutrients Of Eukaryotic Cellsmentioning

confidence: 99%

“…Today, LDs are recognized as complex organelles and much is known about their key role in overseeing a variety of intracellular and environmental stresses, far beyond their main contribution to nutrient administration 4,21,155 . The use of novel systematic molecular profiling approaches, capable of revealing within the LD proteome non‐intuitive systems‐level relationships, decisively shifted the paradigm 41 . Although the presence of antiviral and antibacterial proteins on LDs was described long ago, 9,11 recent work from a number of different groups, including some high‐throughput analyses, has illuminated the complex and bidirectional relationship between LDs and invaders 12,42,79,149,156 .…”

Section: Concluding Remarks Open Questions and Future Directionsmentioning

confidence: 99%

See 2 more Smart Citations

Defensive‐lipid droplets: Cellular organelles designed for antimicrobial immunity

Safi

Sánchez-Álvarez

Bosch

et al. 2023

Immunological Reviews

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SummaryMicrobes have developed many strategies to subvert host organisms, which, in turn, evolved several innate immune responses. As major lipid storage organelles of eukaryotes, lipid droplets (LDs) are an attractive source of nutrients for invaders. Intracellular viruses, bacteria, and protozoan parasites induce and physically interact with LDs, and the current view is that they “hijack” LDs to draw on substrates for host colonization. This dogma has been challenged by the recent demonstration that LDs are endowed with a protein‐mediated antibiotic activity, which is upregulated in response to danger signals and sepsis. Dependence on host nutrients could be a generic “Achilles’ heel” of intracellular pathogens and LDs a suitable chokepoint harnessed by innate immunity to organize a front‐line defense. Here, we will provide a brief overview of the state of the conflict and discuss potential mechanisms driving the formation of the ‘defensive‐LDs’ functioning as hubs of innate immunity.

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Lipid droplets provide metabolic flexibility for cancer progression

Safi,

Menéndez,

Pol

2024

FEBS Letters

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A hallmark of cancer cells is their remarkable ability to efficiently adapt to favorable and hostile environments. Due to a unique metabolic flexibility, tumor cells can grow even in the absence of extracellular nutrients or in stressful scenarios. To achieve this, cancer cells need large amounts of lipids to build membranes, synthesize lipid‐derived molecules, and generate metabolic energy in the absence of other nutrients. Tumor cells potentiate strategies to obtain lipids from other cells, metabolic pathways to synthesize new lipids, and mechanisms for efficient storage, mobilization, and utilization of these lipids. Lipid droplets (LDs) are the organelles that collect and supply lipids in eukaryotes and it is increasingly recognized that the accumulation of LDs is a new hallmark of cancer cells. Furthermore, an active role of LD proteins in processes underlying tumorigenesis has been proposed. Here, by focusing on three major classes of LD‐resident proteins (perilipins, lipases, and acyl‐CoA synthetases), we provide an overview of the contribution of LDs to cancer progression and discuss the role of LD proteins during the proliferation, invasion, metastasis, apoptosis, and stemness of cancer cells.

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Insights Into the Biogenesis and Emerging Functions of Lipid Droplets From Unbiased Molecular Profiling Approaches

Cited by 13 publications

References 307 publications

The TOR signaling pathway regulates vegetative development, aflatoxin biosynthesis, and pathogenicity inAspergillus flavus

The TOR signaling pathway regulates vegetative development, aflatoxin biosynthesis, and pathogenicity inAspergillus flavus

Defensive‐lipid droplets: Cellular organelles designed for antimicrobial immunity

Lipid droplets provide metabolic flexibility for cancer progression

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