scholarly journals Autophagosomes contribute to intracellular lipid distribution in enterocytes

2014 ◽  
Vol 25 (1) ◽  
pp. 118-132 ◽  
Author(s):  
Salem Ait Khaldoun ◽  
Marc-Alexandre Emond-Boisjoly ◽  
Danielle Chateau ◽  
Véronique Carrière ◽  
Michel Lacasa ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Lipid Homeostasis ◽  
Coat Proteins ◽  
Cellular Lipid ◽  
Intracellular Lipid ◽  
Lipid Trafficking ◽  
Complex Lipid ◽  
Lipid Micelles ◽  
Er Membrane

Enterocytes, the intestinal absorptive cells, have to deal with massive alimentary lipids upon food consumption. They orchestrate complex lipid-trafficking events that lead to the secretion of triglyceride-rich lipoproteins and/or the intracellular transient storage of lipids as lipid droplets (LDs). LDs originate from the endoplasmic reticulum (ER) membrane and are mainly composed of a triglyceride (TG) and cholesterol-ester core surrounded by a phospholipid and cholesterol monolayer and specific coat proteins. The pivotal role of LDs in cellular lipid homeostasis is clearly established, but processes regulating LD dynamics in enterocytes are poorly understood. Here we show that delivery of alimentary lipid micelles to polarized human enterocytes induces an immediate autophagic response, accompanied by phosphatidylinositol-3-phosphate appearance at the ER membrane. We observe a specific and rapid capture of newly synthesized LD at the ER membrane by nascent autophagosomal structures. By combining pharmacological and genetic approaches, we demonstrate that autophagy is a key player in TG targeting to lysosomes. Our results highlight the yet-unraveled role of autophagy in the regulation of TG distribution, trafficking, and turnover in human enterocytes.

scholarly journals Recruitment of Peroxin14 to lipid droplets affects triglyceride storage in Drosophila

2021 ◽  
Author(s):  
Matthew Anderson-Baron ◽  
Kazuki Ueda ◽  
Julie Haskins ◽  
Sarah C Hughes ◽  
Andrew Simmonds
Keyword(s):  
Neutral Lipid ◽  
Lipid Droplet ◽  
Functional Role ◽  
Lipid Droplets ◽  
Droplet Surface ◽  
Lipid Homeostasis ◽  
Cellular Lipid ◽  
Peroxisome Biogenesis ◽  
Drosophila Cells

The activity of multiple organelles must be coordinated to ensure cellular lipid homeostasis. This includes the peroxisomes which metabolise certain lipids and lipid droplets which act as neutral lipid storage centres. Direct organellar contact between peroxisomes and lipid droplets has been observed, and interaction between proteins associated with the membranes of these organelles has been shown, but the functional role of these interactions is not clear. In Drosophila cells, we identified a novel localization of a subset of three transmembrane Peroxin proteins (Peroxin3, Peroxin13, and Peroxin14), normally required for peroxisome biogenesis, to newly formed lipid droplets. This event was not linked to significant changes in peroxisome size or number, nor was recruitment of other Peroxin proteins or mature peroxisomes observed. The presence of these Peroxin proteins at lipid droplets influences their function as changes in the relative levels of Peroxin14 associated with the lipid droplet surface directly affected the presence of regulatory perilipin and lipases with corresponding effects on triglyceride storage.

scholarly journals A Decade of Mighty Lipophagy: What We Know and What Facts We Need to Know?

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Muhammad Babar Khawar ◽  
Muddasir Hassan Abbasi ◽  
Mussarat Rafiq ◽  
Naila Naz ◽  
Rabia Mehmood ◽  
...  
Keyword(s):  
Cell Death ◽  
Lipid Droplets ◽  
Lysosomal Enzymes ◽  
Lipid Homeostasis ◽  
Cellular Lipid ◽  
Biological Functions ◽  
Lysosomal Function ◽  
Selective Autophagy ◽  
Cellular Components ◽  
Different Levels

Lipids are integral cellular components that act as substrates for energy provision, signaling molecules, and essential constituents of biological membranes along with a variety of other biological functions. Despite their significance, lipid accumulation may result in lipotoxicity, impair autophagy, and lysosomal function that may lead to certain diseases and metabolic syndromes like obesity and even cell death. Therefore, these lipids are continuously recycled and redistributed by the process of selective autophagy specifically termed as lipophagy. This selective form of autophagy employs lysosomes for the maintenance of cellular lipid homeostasis. In this review, we have reviewed the current literature about how lipid droplets (LDs) are recruited towards lysosomes, cross-talk between a variety of autophagy receptors present on LD surface and lysosomes, and lipid hydrolysis by lysosomal enzymes. In addition to it, we have tried to answer most of the possible questions related to lipophagy regulation at different levels. Moreover, in the last part of this review, we have discussed some of the pathological states due to the accumulation of these LDs and their possible treatments under the light of currently available findings.

scholarly journals Lipids Affect the Cryptococcus neoformans-Macrophage Interaction and Promote Nonlytic Exocytosis

2017 ◽  
Vol 85 (12) ◽  
Author(s):  
Sabrina J. Nolan ◽  
Man Shun Fu ◽  
Isabelle Coppens ◽  
Arturo Casadevall
Keyword(s):  
Oleic Acid ◽  
Cryptococcus Neoformans ◽  
Lipid Droplets ◽  
Fungal Pathogens ◽  
Cellular Lipid ◽  
Content Type ◽  
Acid Supplementation

ABSTRACT Many microbes exploit host cellular lipid droplets during the host-microbe interaction, but this phenomenon has not been extensively studied for fungal pathogens. In this study, we analyzed the role of lipid droplets during the interaction of Cryptococcus neoformans with macrophages in the presence and the absence of exogenous lipids, in particular, oleate. The addition of oleic acid increased the frequency of lipid droplets in both C. neoformans and macrophages. C. neoformans responded to oleic acid supplementation by faster growth inside and outside macrophages. Fungal cells were able to harvest lipids from macrophage lipid droplets. Supplementation of C. neoformans and macrophages with oleic acid significantly increased the rate of nonlytic exocytosis while having no effect on lytic exocytosis. The process for lipid modulation of nonlytic exocytosis was associated with actin changes in macrophages. In summary, C. neoformans harvests lipids from macrophages, and the C. neoformans-macrophage interaction is modulated by exogenous lipids, providing a new tool for studying nonlytic exocytosis.

scholarly journals Exon 9-deleted CETP inhibits full length-CETP synthesis and promotes cellular triglyceride storage

2020 ◽  
Vol 61 (3) ◽  
pp. 422-431 ◽  
Author(s):  
Lahoucine Izem ◽  
Yan Liu ◽  
Richard E. Morton
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Full Length ◽  
Intracellular Lipid ◽  
Transfer Protein ◽  
Lipid Phenotype ◽  
Exon 9 ◽  
And Storage

Cholesteryl ester transfer protein (CETP) exists as full-length (FL) and exon 9 (E9)-deleted isoforms. The function of E9-deleted CETP is poorly understood. Here, we investigated the role of E9-deleted CETP in regulating the secretion of FL-CETP by cells and explored its possible role in intracellular lipid metabolism. CETP overexpression in cells that naturally express CETP confirmed that E9-deleted CETP is not secreted, and showed that cellular FL- and E9-deleted CETP form an isolatable complex. Coexpression of CETP isoforms lowered cellular levels of both proteins and impaired FL-CETP secretion. These effects were due to reduced synthesis of both isoforms; however, the predominate consequence of FL- and E9-deleted CETP coexpression is impaired FL-CETP synthesis. We reported previously that reducing both CETP isoforms or overexpressing FL-CETP impairs cellular triglyceride (TG) storage. To investigate this further, E9-deleted CETP was expressed in SW872 cells that naturally synthesize CETP and in mouse 3T3-L1 cells that do not. E9-deleted CETP overexpression stimulated SW872 triglyceride synthesis and increased stored TG 2-fold. Expression of E9-deleted CETP in mouse 3T3-L1 cells produced a similar lipid phenotype. In vitro, FL-CETP promotes the transfer of TG from ER-enriched membranes to lipid droplets. E9-deleted CETP also promoted this transfer, although less effectively, and it inhibited the transfer driven by FL-CETP. We conclude that FL- and E9-deleted CETP isoforms interact to mutually decrease their intracellular levels and impair FL-CETP secretion by reducing CETP biosynthesis. E9-deleted CETP, like FL-CETP, alters cellular TG metabolism and storage but in a contrary manner.

scholarly journals Direct lysosome-based autophagy of lipid droplets in hepatocytes

2020 ◽  
Vol 117 (51) ◽  
pp. 32443-32452
Author(s):  
Ryan J. Schulze ◽  
Eugene W. Krueger ◽  
Shaun G. Weller ◽  
Katherine M. Johnson ◽  
Carol A. Casey ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Lipid Droplets ◽  
Critical Role ◽  
Specific Protein ◽  
Lipid Homeostasis ◽  
Dynamic Interactions ◽  
Double Membrane ◽  
Live Cell Microscopy ◽  
Cell Microscopy

Hepatocytes metabolize energy-rich cytoplasmic lipid droplets (LDs) in the lysosome-directed process of autophagy. An organelle-selective form of this process (macrolipophagy) results in the engulfment of LDs within double-membrane delimited structures (autophagosomes) before lysosomal fusion. Whether this is an exclusive autophagic mechanism used by hepatocytes to catabolize LDs is unclear. It is also unknown whether lysosomes alone might be sufficient to mediate LD turnover in the absence of an autophagosomal intermediate. We performed live-cell microscopy of hepatocytes to monitor the dynamic interactions between lysosomes and LDs in real-time. We additionally used a fluorescent variant of the LD-specific protein (PLIN2) that exhibits altered fluorescence in response to LD interactions with the lysosome. We find that mammalian lysosomes and LDs undergo interactions during which proteins and lipids can be transferred from LDs directly into lysosomes. Electron microscopy (EM) of primary hepatocytes or hepatocyte-derived cell lines supports the existence of these interactions. It reveals a dramatic process whereby the lipid contents of the LD can be “extruded” directly into the lysosomal lumen under nutrient-limited conditions. Significantly, these interactions are not affected by perturbations to crucial components of the canonical macroautophagy machinery and can occur in the absence of double-membrane lipoautophagosomes. These findings implicate the existence of an autophagic mechanism used by mammalian cells for the direct transfer of LD components into the lysosome for breakdown. This process further emphasizes the critical role of lysosomes in hepatic LD catabolism and provides insights into the mechanisms underlying lipid homeostasis in the liver.

scholarly journals The yeast FIT2 homologs are necessary to maintain cellular proteostasis and membrane lipid homeostasis

2020 ◽  
Vol 133 (21) ◽  
pp. jcs248526 ◽  
Author(s):  
Wei Sheng Yap ◽  
Peter Shyu ◽  
Maria Laura Gaspar ◽  
Stephen A. Jesch ◽  
Charlie Marvalim ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Endoplasmic Reticulum ◽  
Lipid Droplets ◽  
Membrane Lipid ◽  
Model System ◽  
Lipid Homeostasis ◽  
Compensatory Mechanism ◽  
Unfolded Protein ◽  
Protein Response

ABSTRACTLipid droplets (LDs) are implicated in conditions of lipid and protein dysregulation. The fat storage-inducing transmembrane (FIT; also known as FITM) family induces LD formation. Here, we establish a model system to study the role of the Saccharomyces cerevisiae FIT homologues (ScFIT), SCS3 and YFT2, in the proteostasis and stress response pathways. While LD biogenesis and basal endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) remain unaltered in ScFIT mutants, SCS3 was found to be essential for proper stress-induced UPR activation and for viability in the absence of the sole yeast UPR transducer IRE1. Owing to not having a functional UPR, cells with mutated SCS3 exhibited an accumulation of triacylglycerol within the ER along with aberrant LD morphology, suggesting that there is a UPR-dependent compensatory mechanism that acts to mitigate lack of SCS3. Additionally, SCS3 was necessary to maintain phospholipid homeostasis. Strikingly, global protein ubiquitylation and the turnover of both ER and cytoplasmic misfolded proteins is impaired in ScFITΔ cells, while a screen for interacting partners of Scs3 identifies components of the proteostatic machinery as putative targets. Together, our data support a model where ScFITs play an important role in lipid metabolism and proteostasis beyond their defined roles in LD biogenesis.This article has an associated First Person interview with the first author of the paper.

scholarly journals A sterol-enriched vacuolar microdomain mediates stationary phase lipophagy in budding yeast

2014 ◽  
Vol 206 (3) ◽  
pp. 357-366 ◽  
Author(s):  
Chao-Wen Wang ◽  
Yu-Hsuan Miao ◽  
Yi-Shun Chang
Keyword(s):  
Endoplasmic Reticulum ◽  
Stationary Phase ◽  
Lipid Droplets ◽  
Physiological State ◽  
Lipid Homeostasis ◽  
Cellular Lipid ◽  
Sterol Esters ◽  
Selective Autophagy ◽  
The Core ◽  
Atg Proteins

Stationary phase (stat-phase) is a poorly understood physiological state under which cells arrest proliferation and acquire resistance to multiple stresses. Lipid droplets (LDs), organelles specialized for cellular lipid homeostasis, increase in size and number at the onset of stat-phase. However, little is known about the dynamics of LDs under this condition. In this paper, we reveal the passage of LDs from perinuclear endoplasmic reticulum association to entry into vacuoles during the transition to stat-phase. We show that the process requires the core autophagy machinery and a subset of autophagy-related (Atg) proteins involved in selective autophagy. Notably, the process that we term stat-phase lipophagy is mediated through a sterol-enriched vacuolar microdomain whose formation and integrity directly affect LD translocation. Intriguingly, cells defective in stat-phase lipophagy showed disrupted vacuolar microdomains, implying that LD contents, likely sterol esters, contribute to the maintenance of vacuolar microdomains. Together, we propose a feed-forward loop in which lipophagy stimulates vacuolar microdomain formation, which in turn promotes lipophagy during stat-phase.

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