scholarly journals Lipid droplet–mediated ER homeostasis regulates autophagy and cell survival during starvation

2016 ◽  
Vol 212 (6) ◽  
pp. 621-631 ◽  
Author(s):  
Ariadna P. Velázquez ◽  
Takashi Tatsuta ◽  
Ruben Ghillebert ◽  
Ingmar Drescher ◽  
Martin Graef
Keyword(s):  
Cell Survival ◽  
Lipid Droplets ◽  
Metabolic Diseases ◽  
De Novo ◽  
Phospholipid Composition ◽  
Yeast Cells ◽  
Lipid Homeostasis ◽  
Er Homeostasis ◽  
Insight Into ◽  
Catabolic Process

Lipid droplets (LDs) are conserved organelles for intracellular neutral lipid storage. Recent studies suggest that LDs function as direct lipid sources for autophagy, a central catabolic process in homeostasis and stress response. Here, we demonstrate that LDs are dispensable as a membrane source for autophagy, but fulfill critical functions for endoplasmic reticulum (ER) homeostasis linked to autophagy regulation. In the absence of LDs, yeast cells display alterations in their phospholipid composition and fail to buffer de novo fatty acid (FA) synthesis causing chronic stress and morphologic changes in the ER. These defects compromise regulation of autophagy, including formation of multiple aberrant Atg8 puncta and drastically impaired autophagosome biogenesis, leading to severe defects in nutrient stress survival. Importantly, metabolically corrected phospholipid composition and improved FA resistance of LD-deficient cells cure autophagy and cell survival. Together, our findings provide novel insight into the complex interrelation between LD-mediated lipid homeostasis and the regulation of autophagy potentially relevant for neurodegenerative and metabolic diseases.

scholarly journals Friend or Foe: Lipid Droplets as Organelles for Protein and Lipid Storage in Cellular Stress Response, Aging and Disease

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5053
Author(s):  
Florian Geltinger ◽  
Lukas Schartel ◽  
Markus Wiederstein ◽  
Julia Tevini ◽  
Elmar Aigner ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Metabolic Diseases ◽  
Cellular Stress ◽  
Lipid Storage ◽  
Fine Tuning ◽  
Cellular Stress Response ◽  
Lipid Homeostasis ◽  
Storage Site ◽  
Cellular Detoxification ◽  
Storage Organelle

Lipid droplets (LDs) were considered as a mere lipid storage organelle for a long time. Recent evidence suggests that LDs are in fact distinct and dynamic organelles with a specialized proteome and functions in many cellular roles. As such, LDs contribute to cellular signaling, protein and lipid homeostasis, metabolic diseases and inflammation. In line with the multitude of functions, LDs interact with many cellular organelles including mitochondria, peroxisomes, lysosomes, the endoplasmic reticulum and the nucleus. LDs are highly mobile and dynamic organelles and impaired motility disrupts the interaction with other organelles. The reduction of interorganelle contacts results in a multitude of pathophysiologies and frequently in neurodegenerative diseases. Contacts not only supply lipids for β-oxidation in mitochondria and peroxisomes, but also may include the transfer of toxic lipids as well as misfolded and harmful proteins to LDs. Furthermore, LDs assist in the removal of protein aggregates when severe proteotoxic stress overwhelms the proteasomal system. During imbalance of cellular lipid homeostasis, LDs also support cellular detoxification. Fine-tuning of LD function is of crucial importance and many diseases are associated with dysfunctional LDs. We summarize the current understanding of LDs and their interactions with organelles, providing a storage site for harmful proteins and lipids during cellular stress, aging inflammation and various disease states.

scholarly journals Actin cytoskeletal inhibitor 19,20-epoxycytochalasin Q sensitizes yeast cells lacking ERG6 through actin-targeting and secondarily through disruption of lipid homeostasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kwanrutai Watchaputi ◽  
Pichayada Somboon ◽  
Nipatthra Phromma-in ◽  
Khanok Ratanakhanokchai ◽  
Nitnipa Soontorngun
Keyword(s):  
Lipid Droplets ◽  
Wild Type Strain ◽  
Yeast Cells ◽  
Lipid Homeostasis ◽  
Ergosterol Biosynthesis ◽  
Valuable Insight ◽  
Wild Type ◽  
Antifungal Property ◽  
Primary Target ◽  
Very High

AbstractRepetitive uses of antifungals result in a worldwide crisis of drug resistance; therefore, natural fungicides with minimal side-effects are currently sought after. This study aimed to investigate antifungal property of 19, 20-epoxycytochalasin Q (ECQ), derived from medicinal mushroom Xylaria sp. BCC 1067 of tropical forests. In a model yeast Saccharomyces cerevisiae, ECQ is more toxic in the erg6∆ strain, which has previously been shown to allow higher uptake of many hydrophilic toxins. We selected one pathway to study the effects of ECQ at very high levels on transcription: the ergosterol biosynthesis pathway, which is unlikely to be the primary target of ECQ. Ergosterol serves many functions that cholesterol does in human cells. ECQ’s transcriptional effects were correlated with altered sterol and triacylglycerol levels. In the ECQ-treated Δerg6 strain, which presumably takes up far more ECQ than the wild-type strain, there was cell rupture. Increased actin aggregation and lipid droplets assembly were also found in the erg6∆ mutant. Thereby, ECQ is suggested to sensitize yeast cells lacking ERG6 through actin-targeting and consequently but not primarily led to disruption of lipid homeostasis. Investigation of cytochalasins may provide valuable insight with potential biopharmaceutical applications in treatments of fungal infection, cancer or metabolic disorder.

scholarly journals Deregulation of Lipid Homeostasis: A Fa(c)t in the Development of Metabolic Diseases

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2605
Author(s):  
Sabina Cisa-Wieczorek ◽  
María Isabel Hernández-Alvarez
Keyword(s):  
Human Health ◽  
Mammalian Cells ◽  
Metabolic Diseases ◽  
De Novo ◽  
Dietary Lipids ◽  
Lipid Homeostasis ◽  
Published Data ◽  
Beneficial Effects ◽  
De Novo Biosynthesis

Lipids are important molecules for human health. The quantity and quality of fats consumed in the diet have important effects on the modulation of both the natural biosynthesis and degradation of lipids. There is an important number of lipid-failed associated metabolic diseases and an increasing number of studies suggesting that certain types of lipids might be beneficial to the treatment of many metabolic diseases. The aim of the present work is to expose an overview of de novo biosynthesis, storage, and degradation of lipids in mammalian cells, as well as, to review the published data describing the beneficial effects of these processes and the potential of some dietary lipids to improve metabolic diseases.

scholarly journals Lipid perturbation-activated IRE-1 modulates autophagy and lipolysis during endoplasmic reticulum stress

2018 ◽  
Author(s):  
Jhee Hong Koh ◽  
Lei Wang ◽  
Caroline Beaudoin-Chabot ◽  
Guillaume Thibault
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Lipid Droplet ◽  
Metabolic Diseases ◽  
Phospholipid Composition ◽  
Emerging Diseases ◽  
Lipid Homeostasis ◽  
Dependent Manner ◽  
Proteotoxic Stress

ABSTRACTMetabolic disorders such as obesity and nonalcoholic fatty liver disease (NAFLD) are emerging diseases that affect the global population. One facet of these disorders is attributed to the disturbance of membrane lipid composition. Perturbation of endoplasmic reticulum (ER) homeostasis through changes in membrane phospholipid composition results in activation of the unfolded protein response (UPR) and causes dramatic translational and transcriptional changes in the cell. To restore cellular homeostasis, the three highly conserved UPR transducers ATF6, IRE1, and PERK mediate cellular processes upon ER stress. The role of the UPR in proteotoxic stress caused by the accumulation of misfolded proteins is well understood but much less so under lipid perturbation-induced UPR (UPRLP). We found that genetically disrupted phosphatidylcholine synthesis in C. elegans causes, lipid perturbation, lipid droplet accumulation, and induced ER stress, all hallmarks of NAFLD. Transcriptional profiling of UPRLP animals shows a unique subset of genes modulated in an UPR-dependent manner that is unaffected by proteotoxic stress (UPRPT). Among these, we identified autophagy genes bec-1 and lgg-1 and the lipid droplet-associated lipase atgl-1 to be modulated by IRE-1. Considering the important role of lipid homeostasis and how its impairment contributes to the pathology of metabolic diseases, our data uncovers the indispensable role of a fully functional UPR program in regulating lipid homeostasis in the face of chronic ER stress and lipotoxicity.

scholarly journals Lipid droplet autophagy in the yeast Saccharomyces cerevisiae

2014 ◽  
Vol 25 (2) ◽  
pp. 290-301 ◽  
Author(s):  
Tim van Zutphen ◽  
Virginia Todde ◽  
Rinse de Boer ◽  
Martin Kreim ◽  
Harald F. Hofbauer ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Lipid Droplets ◽  
De Novo ◽  
Close Association ◽  
Acid Synthesis ◽  
Lipid Homeostasis ◽  
Yeast Saccharomyces Cerevisiae ◽  
Hormonal Stimulation ◽  
Steryl Esters ◽  
The Core

Cytosolic lipid droplets (LDs) are ubiquitous organelles in prokaryotes and eukaryotes that play a key role in cellular and organismal lipid homeostasis. Triacylglycerols (TAGs) and steryl esters, which are stored in LDs, are typically mobilized in growing cells or upon hormonal stimulation by LD-associated lipases and steryl ester hydrolases. Here we show that in the yeast Saccharomyces cerevisiae, LDs can also be turned over in vacuoles/lysosomes by a process that morphologically resembles microautophagy. A distinct set of proteins involved in LD autophagy is identified, which includes the core autophagic machinery but not Atg11 or Atg20. Thus LD autophagy is distinct from endoplasmic reticulum–autophagy, pexophagy, or mitophagy, despite the close association between these organelles. Atg15 is responsible for TAG breakdown in vacuoles and is required to support growth when de novo fatty acid synthesis is compromised. Furthermore, none of the core autophagy proteins, including Atg1 and Atg8, is required for LD formation in yeast.

scholarly journals Quantitative live-cell PALM reveals nanoscopic Faa4 redistributions and dynamics on lipid droplets during metabolic transitions of yeast

2020 ◽  
Author(s):  
Santosh Adhikari ◽  
Joe Moscatelli ◽  
Elias M. Puchner
Keyword(s):  
Stationary Phase ◽  
Single Molecule ◽  
Lipid Droplets ◽  
Fold Increase ◽  
Diffraction Limit ◽  
Optical Diffraction ◽  
Yeast Cells ◽  
Lipid Homeostasis ◽  
Localization Microscopy ◽  
Live Yeast

AbstractLipid droplets (LDs) are dynamic lipid storage organelles needed for lipid homeostasis. Cells respond to metabolic changes by regulating the spatial distribution of LDs, as well as enzymes required for LD growth and turnover. Due to LD size below the optical diffraction limit, bulk fluorescence microscopy cannot observe the density and dynamics of specific LD enzymes. Here, we employ quantitative photo-activated localization microscopy (PALM) to study the density of the fatty acid activating protein Faa4 on LDs during log, stationary and lag phases in live yeast cells with single-molecule sensitivity and 30 nm resolution. During the log phase LDs co-localize with the Endoplasmic Reticulum (ER) where the highest Faa4 densities are measured. During transition to the stationary phase LDs translocate to the vacuolar surface and lumen with a ~2-fold increased surface area and a ~2.5-fold increase in Faa4 density, suggesting its role in LD expansion. The increased Faa4 density on LDs is caused by its ~5-fold increased expression level. When lipolysis is induced in stationary-phase cells by diluting them for 2 hrs in fresh medium, Faa4 shuttles to the vacuole through the two observed routes of ER- and lipophagy. The observed vacuolar localization of Faa4 may help activating fatty acids for membrane expansion and reduces Faa4 expression to levels found in the log phase.

scholarly journals Peroxisome reintroduction in Hansenula polymorpha requires Pex25 and Rho1

2011 ◽  
Vol 193 (5) ◽  
pp. 885-900 ◽  
Author(s):  
Ruchi Saraya ◽  
Arjen M. Krikken ◽  
Marten Veenhuis ◽  
Ida J. van der Klei
Keyword(s):  
Mutant Strain ◽  
De Novo ◽  
Hansenula Polymorpha ◽  
Protein Family ◽  
Yeast Cells ◽  
Deficient Mutant ◽  
Wild Type ◽  
Double Deletion ◽  
Insight Into

We identified two proteins, Pex25 and Rho1, which are involved in reintroduction of peroxisomes in peroxisome-deficient yeast cells. These are, together with Pex3, the first proteins identified as essential for this process. Of the three members of the Hansenula polymorpha Pex11 protein family—Pex11, Pex25, and Pex11C—only Pex25 was required for reintroduction of peroxisomes into a peroxisome-deficient mutant strain. In peroxisome-deficient pex3 cells, Pex25 localized to structures adjacent to the ER, whereas in wild-type cells it localized to peroxisomes. Pex25 cells were not themselves peroxisome deficient but instead contained a slightly increased number of peroxisomes. Interestingly, pex11 pex25 double deletion cells, in which both peroxisome fission (due to the deletion of PEX11) and reintroduction (due to deletion of PEX25) was blocked, did display a peroxisome-deficient phenotype. Peroxisomes reappeared in pex11 pex25 cells upon synthesis of Pex25, but not of Pex11. Reintroduction in the presence of Pex25 required the function of the GTPase Rho1. These data therefore provide new and detailed insight into factors important for de novo peroxisome formation in yeast.

scholarly journals Lipid droplets are central organelles for meiosis II progression during yeast sporulation

2017 ◽  
Vol 28 (3) ◽  
pp. 440-451 ◽  
Author(s):  
Tzu-Han Hsu ◽  
Rey-Huei Chen ◽  
Yun-Hsin Cheng ◽  
Chao-Wen Wang
Keyword(s):  
Lipid Droplets ◽  
De Novo ◽  
Neutral Lipids ◽  
Spore Wall ◽  
Yeast Cells ◽  
Cytological Evidence ◽  
Major Function ◽  
Cellular Events ◽  
Membrane Morphogenesis ◽  
Wall Assembly

Neutral lipids, predominantly triacylglycerol (TAG) and sterol ester, are stored within the cellular organelles termed lipid droplets (LDs). Although it is believed that the major function of LDs is to supply the cell with energy and membranes, little is known about the cellular events directly involving LDs and their contents. In this study, we provide cytological evidence that LDs form direct contacts with the prospore membrane (PSM) that is synthesized de novo during meiosis II to sequester the dividing nuclei in sporulating yeast. Lipidomic analyses indicate that TAG lipolysis releases free fatty acids at a time that correlates well with meiosis II progression, concomitant with phospholipid remodeling. Mutants lacking TAG or impaired of TAG hydrolysis show spore wall assembly defects, supporting a role for TAG and/or its metabolites in spore wall morphogenesis. Not only does LD integrity influence spore wall assembly, LDs are also essential for other aspects of spore development. Yeast cells lacking LDs are severely defective in PSM growth and organization and display disrupted spindles, producing dead spores or even failing to form spores. Together these results link LD physiology directly to a unique membrane morphogenesis process critical for development.

Upcoming Drifts In Bio-Similars

2020 ◽  
Vol 15 ◽  
Author(s):  
Geeta Aggarwal ◽  
Manju Nagpal ◽  
Ameya Sharma ◽  
Vivek Puri ◽  
Gitika Arora Dhingra
Keyword(s):  
Metabolic Diseases ◽  
Market Competition ◽  
Current Status ◽  
Medicinal Products ◽  
The Past ◽  
Biologic Activity ◽  
Emerging Trends ◽  
Regulatory Guidelines ◽  
Food Drug Administration ◽  
Insight Into

Background: Biopharmaceuticals such as Biologic medicinal products have been in clinical use over the past three decades and have benefited towards the therapy of degenerative and critical metabolic diseases. It is forecasted that market of biologics will be going to increase at a rate of 20% per year, and by 2025, more than ˃ 50% of new drug approvals may be biological products. The increasing utilization of the biologics necessitates for cost control, especially for innovators products that have enjoyed a lengthy period of exclusive use. As the first wave of biopharmaceuticals is expired or set to expire, it has led to various opportunities for the expansion of bio-similars i.e. copied versions of original biologics with same biologic activity. Development of biosimilars is expected to promote market competition, meet worldwide demand, sustain the healthcare systems and maintain the incentives for innovation. Methods: Appraisal of published articles from peer reviewed journals, PubMed literature, latest news and guidelines from European Medicine Agency, US Food Drug Administration (FDA) and India are used to identify data for review. Results: Main insight into the quality requirements concerning biologics, current status of regulation of biosimilars and upcoming challenges lying ahead for the upgrading of marketing authorization of bio-similars has been incorporated. Compiled literature on therapeutic status, regulatory guidelines and the emerging trends and opportunities of biosimilars has been thoroughly stated. Conclusion: Updates on biosimilars will support to investigate the possible impact of bio-similars on healthcare market.

scholarly journals Genomic Characterization Provides an Insight into the Pathogenicity of the Poplar Canker Bacterium Lonsdalea populi

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 246
Author(s):  
Xiaomeng Chen ◽  
Rui Li ◽  
Yonglin Wang ◽  
Aining Li
Keyword(s):  
Genome Sequence ◽  
Extracellular Enzymes ◽  
De Novo ◽  
Whole Genome Sequence ◽  
Hybrid Poplars ◽  
A Genome ◽  
Conserved Genes ◽  
Genomic Characterization ◽  
Molecular Bases ◽  
Insight Into

An emerging poplar canker caused by the gram-negative bacterium, Lonsdalea populi, has led to high mortality of hybrid poplars Populus × euramericana in China and Europe. The molecular bases of pathogenicity and bark adaptation of L. populi have become a focus of recent research. This study revealed the whole genome sequence and identified putative virulence factors of L. populi. A high-quality L. populi genome sequence was assembled de novo, with a genome size of 3,859,707 bp, containing approximately 3434 genes and 107 RNAs (75 tRNA, 22 rRNA, and 10 ncRNA). The L. populi genome contained 380 virulence-associated genes, mainly encoding for adhesion, extracellular enzymes, secretory systems, and two-component transduction systems. The genome had 110 carbohydrate-active enzyme (CAZy)-coding genes and putative secreted proteins. The antibiotic-resistance database annotation listed that L. populi was resistant to penicillin, fluoroquinolone, and kasugamycin. Analysis of comparative genomics found that L. populi exhibited the highest homology with the L. britannica genome and L. populi encompassed 1905 specific genes, 1769 dispensable genes, and 1381 conserved genes, suggesting high evolutionary diversity and genomic plasticity. Moreover, the pan genome analysis revealed that the N-5-1 genome is an open genome. These findings provide important resources for understanding the molecular basis of the pathogenicity and biology of L. populi and the poplar-bacterium interaction.

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