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 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.

scholarly journals Cargo Recognition and Function of Selective Autophagy Receptors in Plants

2021 ◽  
Vol 22 (3) ◽  
pp. 1013
Author(s):  
Shuwei Luo ◽  
Xifeng Li ◽  
Yan Zhang ◽  
Yunting Fu ◽  
Baofang Fan ◽  
...  
Keyword(s):  
Cellular Response ◽  
Plant Responses ◽  
Biological Functions ◽  
Biotic And Abiotic Stresses ◽  
Selective Autophagy ◽  
Evolutionarily Conserved ◽  
Autophagic Degradation ◽  
Species Specific ◽  
And Function ◽  
Cellular Components

Autophagy is a major quality control system for degradation of unwanted or damaged cytoplasmic components to promote cellular homeostasis. Although non-selective bulk degradation of cytoplasm by autophagy plays a role during cellular response to nutrient deprivation, the broad roles of autophagy are primarily mediated by selective clearance of specifically targeted components. Selective autophagy relies on cargo receptors that recognize targeted components and recruit them to autophagosomes through interaction with lapidated autophagy-related protein 8 (ATG8) family proteins anchored in the membrane of the forming autophagosomes. In mammals and yeast, a large collection of selective autophagy receptors have been identified that mediate the selective autophagic degradation of organelles, aggregation-prone misfolded proteins and other unwanted or nonnative proteins. A substantial number of selective autophagy receptors have also been identified and functionally characterized in plants. Some of the autophagy receptors in plants are evolutionarily conserved with homologs in other types of organisms, while a majority of them are plant-specific or plant species-specific. Plant selective autophagy receptors mediate autophagic degradation of not only misfolded, nonactive and otherwise unwanted cellular components but also regulatory and signaling factors and play critical roles in plant responses to a broad spectrum of biotic and abiotic stresses. In this review, we summarize the research on selective autophagy in plants, with an emphasis on the cargo recognition and the biological functions of plant selective autophagy receptors.

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 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.

scholarly journals The Troyer syndrome protein spartin mediates selective autophagy of lipid droplets

2021 ◽  
Author(s):  
Jeeyun Chung ◽  
Joongkyu Park ◽  
Zon Weng Lai ◽  
Talley J. Lambert ◽  
Ruth C. Richards ◽  
...  
Keyword(s):  
Energy Storage ◽  
Motor Cortex ◽  
Hereditary Spastic Paraplegia ◽  
Lipid Droplets ◽  
Molecular Mechanisms ◽  
Lipid Homeostasis ◽  
Spastic Paraplegia ◽  
Selective Autophagy ◽  
Important Pathway ◽  
Syndrome Protein

Lipid droplets (LDs) are crucial organelles for energy storage and lipid homeostasis. Autophagy of LDs is an important pathway for their catabolism, but the molecular mechanisms mediating targeting of LDs for degradation by selective autophagy (lipophagy) are unknown. Here we identify spartin as a receptor localizing to LDs and interacting with core autophagy machinery, and we show that spartin is required to deliver LDs to lysosomes for triglyceride (TG) mobilization. Mutations in SPART (encoding spartin) lead to Troyer syndrome, a form of hereditary spastic paraplegia. We find that interfering with spartin function leads to LD and TG accumulation in motor cortex neurons of mice. Our findings thus identify spartin as a lipophagy receptor and suggest that impaired LD turnover may contribute to Troyer syndrome development.

scholarly journals The dynamic behavior of lipid droplets in the pre-metastatic niche

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chunliang Shang ◽  
Jie Qiao ◽  
Hongyan Guo
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Lipid Droplets ◽  
Metastatic Tumor ◽  
Current Evidence ◽  
Biological Functions ◽  
Metastatic Niche ◽  
Niche Formation

AbstractThe pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.

scholarly journals Autophagy impairment as a key feature for acetaminophen-induced ototoxicity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tong Zhao ◽  
Tihua Zheng ◽  
Huining Yu ◽  
Bo Hua Hu ◽  
Bing Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Lysosomal Enzymes ◽  
Apoptotic Cell ◽  
Cell Damage ◽  
Treatment Strategies ◽  
Explant Culture ◽  
Apoptotic Cell Death ◽  
Lysosomal Dysfunction ◽  
Autophagic Degradation

AbstractMacroautophagy/autophagy is a highly conserved self-digestion pathway that plays an important role in cytoprotection under stress conditions. Autophagy is involved in hepatotoxicity induced by acetaminophen (APAP) in experimental animals and in humans. APAP also causes ototoxicity. However, the role of autophagy in APAP-induced auditory hair cell damage is unclear. In the present study, we investigated autophagy mechanisms during APAP-induced cell death in a mouse auditory cell line (HEI-OC1) and mouse cochlear explant culture. We found that the expression of LC3-II protein and autophagic structures was increased in APAP-treated HEI-OC1 cells; however, the degradation of SQSTM1/p62 protein, the yellow puncta of mRFP-GFP-LC3 fluorescence, and the activity of lysosomal enzymes decreased in APAP-treated HEI-OC1 cells. The degradation of p62 protein and the expression of lysosomal enzymes also decreased in APAP-treated mouse cochlear explants. These data indicate that APAP treatment compromises autophagic degradation and causes lysosomal dysfunction. We suggest that lysosomal dysfunction may be directly responsible for APAP-induced autophagy impairment. Treatment with antioxidant N-acetylcysteine (NAC) partially alleviated APAP-induced autophagy impairment and apoptotic cell death, suggesting the involvement of oxidative stress in APAP-induced autophagy impairment. Inhibition of autophagy by knocking down of Atg5 and Atg7 aggravated APAP-induced ER and oxidative stress and increased apoptotic cell death. This study provides a better understanding of the mechanism responsible for APAP ototoxicity, which is important for future exploration of treatment strategies for the prevention of hearing loss caused by ototoxic medications.

scholarly journals Seipin is required for converting nascent to mature lipid droplets

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Huajin Wang ◽  
Michel Becuwe ◽  
Benjamin E Housden ◽  
Chandramohan Chitraju ◽  
Ashley J Porras ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Lipid Synthesis ◽  
Human Cells ◽  
Lipid Transfer ◽  
Cellular Lipid ◽  
Contact Sites ◽  
Discrete Step

How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation—the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs.

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