Recruitment of Peroxin14 to lipid droplets affects triglyceride storage in Drosophila

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.

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Fretting about fat: a new look at the lipid droplet surface and the roundabout role of Plin2 in cellular lipid storage. Focus on “Direct interaction of Plin2 with lipids on the surface of lipid droplets: a live cell FRET analysis”

AJP Cell Physiology ◽

10.1152/ajpcell.00250.2012 ◽

2012 ◽

Vol 303 (7) ◽

pp. C713-C714 ◽

Cited By ~ 2

Author(s):

Jeffrey S. Elmendorf

Keyword(s):

Lipid Droplet ◽

Lipid Droplets ◽

Direct Interaction ◽

Droplet Surface ◽

Lipid Storage ◽

Live Cell ◽

Cellular Lipid ◽

New Look

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Autophagosomes contribute to intracellular lipid distribution in enterocytes

Molecular Biology of the Cell ◽

10.1091/mbc.e13-06-0324 ◽

2014 ◽

Vol 25 (1) ◽

pp. 118-132 ◽

Cited By ~ 59

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.

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5539161 ◽

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.

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

Infection and Immunity ◽

10.1128/iai.00564-17 ◽

2017 ◽

Vol 85 (12) ◽

Cited By ~ 6

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.

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773 HEPATITIS C VIRUS AND LIPID DROPLETS: ROLE OF SEIPIN IN LIPID DROPLET MATURATION AND VIRAL LIFE CYCLE

Journal of Hepatology ◽

10.1016/s0168-8278(11)60775-7 ◽

2011 ◽

Vol 54 ◽

pp. S311 ◽

Cited By ~ 1

Author(s):

S. Clement ◽

C. Fauvelle ◽

S. Pascarella ◽

S. Conzelmann ◽

V. Kaddai ◽

...

Keyword(s):

Life Cycle ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Lipid Droplet ◽

Lipid Droplets ◽

Viral Life Cycle

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Direct lysosome-based autophagy of lipid droplets in hepatocytes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2011442117 ◽

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.

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Seipin-Mediated Contacts as Gatekeepers of Lipid Flux at the Endoplasmic Reticulum–Lipid Droplet Nexus

Contact ◽

10.1177/2515256420945820 ◽

2020 ◽

Vol 3 ◽

pp. 251525642094582

Author(s):

Veijo T. Salo ◽

Maarit Hölttä-Vuori ◽

Elina Ikonen

Keyword(s):

Endoplasmic Reticulum ◽

Lipid Metabolism ◽

Recent Work ◽

Lipid Droplet ◽

Lipid Droplets ◽

Intimate Relationship

Lipid droplets (LDs) are dynamic cellular hubs of lipid metabolism. While LDs contact a plethora of organelles, they have the most intimate relationship with the endoplasmic reticulum (ER). Indeed, LDs are initially assembled at specialized ER subdomains, and recent work has unraveled an increasing array of proteins regulating ER-LD contacts. Among these, seipin, a highly conserved lipodystrophy protein critical for LD growth and adipogenesis, deserves special attention. Here, we review recent insights into the role of seipin in LD biogenesis and as a regulator of ER-LD contacts. These studies have also highlighted the evolving concept of ER and LDs as a functional continuum for lipid partitioning and pinpointed a role for seipin at the ER-LD nexus in controlling lipid flux between these compartments.

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