scholarly journals Autophagy is required for lipid homeostasis during dark-induced senescence in Arabidopsis

2020 ◽  
Author(s):  
Jessica AS Barros ◽  
Sahar Magen ◽  
Taly Lapidot-Cohen ◽  
Leah Rosental ◽  
Yariv Brotman ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Metabolic Reprogramming ◽  
Eukaryotic Cells ◽  
Lipid Homeostasis ◽  
Evolutionarily Conserved ◽  
Altered Lipid ◽  
Starvation Conditions

Autophagy is an evolutionarily conserved mechanism that mediates the degradation of cytoplasmic components in eukaryotic cells. In plants, autophagy has been extensively associated with the recycling of proteins during carbon starvation conditions. Even tough lipids constitute a significant energy reserve, our understanding of the function of autophagy in the management of cell lipid reserves and components remains fragmented. To further investigate the significance of autophagy in lipid metabolism, we performed an extensive lipidomic characterization of Arabidopsis (Arabidopsis thaliana) autophagy mutants (atg) submitted to dark-induced senescence conditions. Our results revealed an altered lipid profile in atg mutants, suggesting that autophagy affects the homeostasis of multiple lipid components under dark-induced senescence. The acute degradation of chloroplast lipids coupled with the differential accumulation of triacylglycerols (TAGs) and plastoglobuli-related transcripts indicates an alternative metabolic reprogramming towards lipid storage in atg mutants. The imbalance of lipid metabolism compromises the production of cytosolic lipid droplets and the regulation of peroxisomal lipid oxidation pathways in atg mutants.

scholarly journals Lipid Metabolism in Oncology: Why It Matters, How to Research, and How to Treat

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 474
Author(s):  
Yuki Matsushita ◽  
Hayato Nakagawa ◽  
Kazuhiko Koike
Keyword(s):  
Lipid Metabolism ◽  
Cancer Biology ◽  
Cellular Level ◽  
Metabolic Reprogramming ◽  
Glutamine Metabolism ◽  
Cellular Functions ◽  
Altered Lipid Metabolism ◽  
Altered Lipid

Lipids in our body, which are mainly composed of fatty acids, triacylglycerides, sphingolipids, phospholipids, and cholesterol, play important roles at the cellular level. In addition to being energy sources and structural components of biological membranes, several types of lipids serve as signaling molecules or secondary messengers. Metabolic reprogramming has been recognized as a hallmark of cancer, but changes in lipid metabolism in cancer have received less attention compared to glucose or glutamine metabolism. However, recent innovations in mass spectrometry- and chromatography-based lipidomics technologies have increased our understanding of the role of lipids in cancer. Changes in lipid metabolism, so-called “lipid metabolic reprogramming”, can affect cellular functions including the cell cycle, proliferation, growth, and differentiation, leading to carcinogenesis. Moreover, interactions between cancer cells and adjacent immune cells through altered lipid metabolism are known to support tumor growth and progression. Characterization of cancer-specific lipid metabolism can be used to identify novel metabolic targets for cancer treatment, and indeed, several clinical trials are currently underway. Thus, we discuss the latest findings on the roles of lipid metabolism in cancer biology and introduce current advances in lipidomics technologies, focusing on their applications in cancer research.

scholarly journals CBIO-05. LIPID METABOLIC REPROGRAMMING SENSITIZES A MOLECULARLY-DEFINED SUBSET OF GLIOBLASTOMAS TO FERROPTOSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii16-ii16
Author(s):  
Danielle Morrow ◽  
David Nathanson ◽  
Timothy Cloughesy ◽  
Robert Prins ◽  
Nicholas Bayley ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Metabolic Reprogramming ◽  
Membrane Phospholipids ◽  
Molecular Alterations ◽  
Lipidomic Analysis ◽  
Novel Association ◽  
Therapeutic Opportunity ◽  
Dependent Cell ◽  
Main Components

Abstract Cancers, including the universally lethal glioblastoma (GBM), have reprogrammed lipid metabolism to fuel tumor growth. However, the molecular alterations responsible for aberrant lipid metabolism, and the potential for identifying new therapeutic opportunities are not fully understood. To systematically investigate the GBM lipidome, we performed integrated transcriptomic, genomic and shotgun lipidomic analysis of an extensive library of molecularly diverse patient-derived GBM samples. Using this comprehensive approach, we discovered two GBM sub-groups defined by their combined molecular and lipidomic profile. Triacylglycerides (TAGs) enriched in polyunsaturated fatty acids (PUFAs) were among the most significantly altered lipids between the two groups of GBM tumors. TAGs are the main components of lipid droplets, which sequester PUFA-TAGs away from membrane phospholipids where their peroxidation can lead to ferroptosis – a regulated from of PUFA-peroxidation dependent cell death. Accordingly, the GBM subgroup with a depletion of PUFA TAGs showed heightened sensitivity to ferroptosis. Our findings suggest a novel association between specific molecular signatures of GBM, lipid metabolism and ferroptosis. This relationship may present a new therapeutic opportunity to target reprogrammed lipid metabolism in a molecularly-defined subset of GBMs.

scholarly journals DRAM-3 modulates autophagy and promotes cell survival in the absence of glucose

2015 ◽  
Vol 22 (10) ◽  
pp. 1714-1726 ◽  
Author(s):  
M Mrschtik ◽  
J O'Prey ◽  
L Y Lao ◽  
J S Long ◽  
F Beaumatin ◽  
...  
Keyword(s):  
Cell Survival ◽  
Membrane Trafficking ◽  
Clonogenic Survival ◽  
Autophagic Flux ◽  
Normal Tissues ◽  
Atg Proteins ◽  
Dna Damaging Agents ◽  
Evolutionarily Conserved ◽  
Starvation Conditions

Abstract Macroautophagy is a membrane-trafficking process that delivers cytoplasmic constituents to lysosomes for degradation. The process operates under basal conditions as a mechanism to turnover damaged or misfolded proteins and organelles. As a result, it has a major role in preserving cellular integrity and viability. In addition to this basal function, macroautophagy can also be modulated in response to various forms of cellular stress, and the rate and cargoes of macroautophagy can be tailored to facilitate appropriate cellular responses in particular situations. The macroautophagy machinery is regulated by a group of evolutionarily conserved autophagy-related (ATG) proteins and by several other autophagy regulators, which either have tissue-restricted expression or operate in specific contexts. We report here the characterization of a novel autophagy regulator that we have termed DRAM-3 due to its significant homology to damage-regulated autophagy modulator (DRAM-1). DRAM-3 is expressed in a broad spectrum of normal tissues and tumor cells, but different from DRAM-1, DRAM-3 is not induced by p53 or DNA-damaging agents. Immunofluorescence studies revealed that DRAM-3 localizes to lysosomes/autolysosomes, endosomes and the plasma membrane, but not the endoplasmic reticulum, phagophores, autophagosomes or Golgi, indicating significant overlap with DRAM-1 localization and with organelles associated with macroautophagy. In this regard, we further proceed to show that DRAM-3 expression causes accumulation of autophagosomes under basal conditions and enhances autophagic flux. Reciprocally, CRISPR/Cas9-mediated disruption of DRAM-3 impairs autophagic flux confirming that DRAM-3 is a modulator of macroautophagy. As macroautophagy can be cytoprotective under starvation conditions, we also tested whether DRAM-3 could promote survival on nutrient deprivation. This revealed that DRAM-3 can repress cell death and promote long-term clonogenic survival of cells grown in the absence of glucose. Interestingly, however, this effect is macroautophagy-independent. In summary, these findings constitute the primary characterization of DRAM-3 as a modulator of both macroautophagy and cell survival under starvation conditions.

scholarly journals Catching Lipid Droplet Contacts by Proteomics

Contact ◽  
2019 ◽  
Vol 2 ◽  
pp. 251525641985918 ◽  
Author(s):  
Natalie Krahmer ◽  
Matthias Mann
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Metabolic Disorders ◽  
State Of The Art ◽  
Contact Site ◽  
Steatotic Liver ◽  
Pathological Conditions ◽  
Obesity Research ◽  
Cellular Compartments

Lipid droplets (LDs), important organelles for energy storage and involved in the development of metabolic disorders, are extremely dynamic and interact with many other cellular compartments to orchestrate lipid metabolism. Little is known about how these organelle contacts are changed according to cellular needs and functions under different metabolic and pathological conditions and which proteins regulate this. Here, we summarize recent exciting discoveries about the reorganization of organelle contacts in steatotic liver, including the identification of novel LD contact site proteins in cell lines and in animals. We also discuss state of the art proteomics workflows that enable the characterization of LD-organelle contacts and tethering proteins and give an outlook how this can inform obesity research.

Characterization of an acyl-CoA synthetase from Arabidopsis thaliana

2000 ◽  
Vol 28 (6) ◽  
pp. 957-958 ◽  
Author(s):  
J. A. Schnurr ◽  
J. Shockey ◽  
John Browse
Keyword(s):  
Arabidopsis Thaliana ◽  
Lipid Metabolism ◽  
Reverse Genetics ◽  
Cell Function ◽  
De Novo ◽  
Plant Biotechnology ◽  
Plant Lipid ◽  
Oilseed Crops ◽  
Isolation And Characterization

One of the major goals of modern plant biotechnology is to manipulate lipid metabolism in oilseed crops to produce new and improved edible and industrial vegetable oils. Lipids constitute the structural components of cellular membranes and act as sources of energy for the germinating seed and are therefore essential to plant cell function. Both de novo synthesis and modification of existing lipids are dependent on the activity of acyl-CoA synthetases (ACSs). To date, ACSs have been recalcitrant to traditional methods of purification due to their association with membranes. In our laboratory, several isoforms of ACSs have been identified in Arabidopsis thaliana. Reverse genetics allowed us to identify a mutant containing a transfer DNA-interrupted ACS gene. Results will be presented that describe the isolation and characterization of this mutant. The elucidation of the specific roles of ACSs will lead to a greater understanding of plant lipid metabolism.

scholarly journals Peroxisomal-PEX5 Controls Fasting-Induced Lipolysis

Contact ◽  
2020 ◽  
Vol 3 ◽  
pp. 251525642096030
Author(s):  
Ji Seul Han ◽  
Kyung Hee Han ◽  
Jae Bum Kim
Keyword(s):  
Lipid Metabolism ◽  
Energy Metabolism ◽  
Knockout Mice ◽  
Lipid Droplets ◽  
Physical Contact ◽  
Lipid Homeostasis ◽  
Subcellular Organelles ◽  
Nutritional Deprivation ◽  
Spatiotemporal Regulation ◽  
Lipid Metabolites

Lipid droplets (LDs) are dynamic subcellular organelles which play critical roles for lipid homeostasis upon change of nutritional state. Although several organelles such as mitochondria and peroxisomes are involved in lipid metabolism, physiological roles and mediators involved in the spatiotemporal regulation of these subcellular organelles for energy metabolism has largely remained elusive. Our recent study implicates the importance of peroxisomes in the translocation of lipases onto LDs upon fasting cues. Also, we found that peroxisomal protein PEX5 modulates PKA-induced lipolysis by escorting ATGL toward LDs. This is accompanied by KIFC3-mediated migration of peroxisomes, leading to the physical contact between peroxisomes and LDs. In adipocyte-specific PEX5-knockout mice, fasting induced lipolysis is attenuated due to defective ATGL recruitment onto LDs. These results show that PEX5 plays a pivotal role in PKA induced lipolysis that occurs upon nutritional deprivation. We further speculate that the contact between LDs and peroxisomes could facilitate lipid metabolism via exchange of lipid metabolites between the organelles in response to nutritional changes.

scholarly journals Reserve lipids and plant autophagy

2020 ◽  
Vol 71 (10) ◽  
pp. 2854-2861 ◽  
Author(s):  
Céline Masclaux-Daubresse ◽  
Sabine d’Andrea ◽  
Isabelle Bouchez ◽  
Jean-Luc Cacas
Keyword(s):  
Lipid Droplets ◽  
Eukaryotic Cells ◽  
Lipid Homeostasis ◽  
Recent Developments ◽  
The Relationship ◽  
Universal Mechanism

Abstract Autophagy is a universal mechanism that facilitates the degradation of unwanted cytoplasmic components in eukaryotic cells. In this review, we highlight recent developments in the investigation of the role of autophagy in lipid homeostasis in plants by comparison with algae, yeast, and animals. We consider the storage compartments that form the sources of lipids in plants, and the roles that autophagy plays in the synthesis of triacylglycerols and in the formation and maintenance of lipid droplets. We also consider the relationship between lipids and the biogenesis of autophagosomes, and the role of autophagy in the degradation of lipids in plants.

scholarly journals Atg17 Functions in Cooperation with Atg1 and Atg13 in Yeast Autophagy

2005 ◽  
Vol 16 (5) ◽  
pp. 2544-2553 ◽  
Author(s):  
Yukiko Kabeya ◽  
Yoshiaki Kamada ◽  
Misuzu Baba ◽  
Hirosato Takikawa ◽  
Mitsuru Sasaki ◽  
...  
Keyword(s):  
Kinase Activity ◽  
Biochemical Characterization ◽  
Eukaryotic Cells ◽  
Autophagosome Formation ◽  
Yeast Saccharomyces Cerevisiae ◽  
Starvation Condition ◽  
Mutant Cells ◽  
Two Hybrid ◽  
Starvation Conditions

In eukaryotic cells, nutrient starvation induces the bulk degradation of cellular materials; this process is called autophagy. In the yeast Saccharomyces cerevisiae, most of the ATG (autophagy) genes are involved in not only the process of degradative autophagy, but also a biosynthetic process, the cytoplasm to vacuole (Cvt) pathway. In contrast, the ATG17 gene is required specifically in autophagy. To better understand the function of Atg17, we have performed a biochemical characterization of the Atg17 protein. We found that the atg17Δ mutant under starvation condition was largely impaired in autophagosome formation and only rarely contained small autophagosomes, whose size was less than one-half of normal autophagosomes in diameter. Two-hybrid analyses and coimmunoprecipitation experiments demonstrated that Atg17 physically associates with Atg1-Atg13 complex, and this binding was enhanced under starvation conditions. Atg17-Atg1 binding was not detected in atg13Δ mutant cells, suggesting that Atg17 interacts with Atg1 through Atg13. A point mutant of Atg17, Atg17C24R, showed reduced affinity for Atg13, resulting in impaired Atg1 kinase activity and significant defects in autophagy. Taken together, these results indicate that Atg17-Atg13 complex formation plays an important role in normal autophagosome formation via binding to and activating the Atg1 kinase.

scholarly journals Importance of γ-secretase in the regulation of liver X receptor and cellular lipid metabolism

2020 ◽  
Vol 3 (6) ◽  
pp. e201900521 ◽  
Author(s):  
Esteban Gutierrez ◽  
Dieter Lütjohann ◽  
Anja Kerksiek ◽  
Marietta Fabiano ◽  
Naoto Oikawa ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Amyloid Precursor Protein ◽  
Lipid Droplets ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Lipid Homeostasis ◽  
Amyloid Β Peptide ◽  
Cellular Lipid ◽  
Additional Protein ◽  
X Receptors

Presenilins (PS) are the catalytic components of γ-secretase complexes that mediate intramembrane proteolysis. Mutations in the PS genes are a major cause of familial early-onset Alzheimer disease and affect the cleavage of the amyloid precursor protein, thereby altering the production of the amyloid β-peptide. However, multiple additional protein substrates have been identified, suggesting pleiotropic functions of γ-secretase. Here, we demonstrate that inhibition of γ-secretase causes dysregulation of cellular lipid homeostasis, including up-regulation of liver X receptors, and complex changes in the cellular lipid composition. Genetic and pharmacological inhibition of γsecretase leads to strong accumulation of cytoplasmic lipid droplets, associated with increased levels of acylglycerols, but lowered cholesteryl esters. Furthermore, accumulation of lipid droplets was augmented by increasing levels of amyloid precursor protein C-terminal fragments, indicating a critical involvement of this γ-secretase substrate. Together, these data provide a mechanism that functionally connects γ-secretase activity to cellular lipid metabolism. These effects were also observed in human astrocytic cells, indicating an important function of γ-secretase in cells critical for lipid homeostasis in the brain.

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