Selective autophagy of intracellular organelles: Recent research advances

Theranostics, Journal Year: 2020, Volume and Issue: 11(1), P. 222 - 256

Published: Oct. 9, 2020

Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants yeast). Autophagy generally induced by stress, such as oxygen-, energy- amino acid-deprivation, irradiation, drugs, etc. In addition to non-selective bulk degradation, autophagy also occurs selective manner, recycling specific mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes lipid droplets (LDs). This capability makes major maintaining cellular homeostasis. The dysfunction of implicated neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, Considering importance cell biology, we systemically review recent advances our understanding this its regulatory mechanisms. We emphasize 'cargo-ligand-receptor' model for organelles components yeast mammals, with focus on mitophagy ER-phagy, which are finely described types autophagy. Additionally, highlight unanswered questions field, helping readers research blind spots need be broken.

Language: Английский

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Lipid droplet biogenesis and functions in health and disease

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 19(8), P. 443 - 459

Published: May 23, 2023

Language: Английский

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ATGL is a biosynthetic enzyme for fatty acid esters of hydroxy fatty acids

Nature, Journal Year: 2022, Volume and Issue: 606(7916), P. 968 - 975

Published: June 8, 2022

Abstract Branched fatty acid (FA) esters of hydroxy FAs (HFAs; FAHFAs) are recently discovered lipids that conserved from yeast to mammals 1,2 . A subfamily, palmitic stearic acids (PAHSAs), anti-inflammatory and anti-diabetic 1,3 Humans mice with insulin resistance have lower PAHSA levels in subcutaneous adipose tissue serum 1 administration improves glucose tolerance sensitivity reduces inflammation obesity, diabetes immune-mediated diseases 1,4–7 The enzyme(s) responsible for FAHFA biosynthesis vivo remains unknown. Here we identified triglyceride lipase (ATGL, also known as patatin-like phospholipase domain containing 2 (PNPLA2)) a candidate biosynthetic enzyme FAHFAs using chemical biology proteomics. We recombinant ATGL uses transacylation reaction esterifies an HFA FA (TG) or diglyceride produce FAHFAs. Overexpression wild-type, but not catalytically dead, increases biosynthesis. Chemical inhibition genetic deletion Atgl inhibits the FAHFA-TG. Levels endogenous nascent FAHFA-TGs 80–90 per cent which is knocked out specifically tissue. Increasing TG by upregulating diacylglycerol acyltransferase (DGAT) activity promotes biosynthesis, decreasing DGAT it, reinforcing TGs precursors. transacylase present human underscoring its potential clinical relevance. In summary, first, our knowledge, catalyses formation ester bond mammals. Whereas well known, data establish paradigm shift demonstrating biologically important.

Language: Английский

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A twist of FATe: Lipid droplets and inflammatory lipid mediators

Biochimie, Journal Year: 2019, Volume and Issue: 169, P. 69 - 87

Published: Nov. 28, 2019

Lipid droplets are fat storage organelles present in most eukaryotic cells. They consist of a neutral lipid core containing mostly triglycerides and sterol esters covered by monolayer phospholipids, wherein numerous proteins embedded. In the cell, have dynamic life cycle, rapidly altering their size, location, protein composition response to environmental stimuli cell state. primarily involved coordination metabolism with cellular requirements for energy production, membrane homeostasis growth. However, they also directly or indirectly engaged signalling pathways. On one hand, sequester lipids thereby limiting availability participation other lipolytic machinery provides highly regulated, on-demand source lipids: derived from core, phospholipid monolayer, act as mediators converted into ones. fact, emerging studies suggest that these essential various stress mechanisms, including inflammation immunity, acting hubs integrate metabolic inflammatory processes. Here, we discuss ways which regulate fatty acids activation pathways production polyunsaturated acid-derived mediators. We focus particular on recent discoveries immune cells adipose tissue revealed an intricate relationship between may be relevant tissues human diseases.

Language: Английский

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Lipid accumulation and oxidation in glioblastoma multiforme

Scientific Reports, Journal Year: 2019, Volume and Issue: 9(1)

Published: Dec. 20, 2019

Glioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumor in adults. Despite multimodal standard treatments for GBM, median survival still about one year. Analysis of tissues from GBM patients shows that lipid droplets are highly enriched while undetectable normal tissues, yet identity functions species not well understood. The aims present work to determine how utilizes fatty acids, assess their roles proliferation. Treatment U138 cells with a monounsaturated acid, oleic induces accumulation perilipin 2-coated containing triglycerides C18:1 increases acid oxidation. Interestingly, also glucose utilization proliferation cells. In contrast, pharmacologic inhibition monoacylglycerol lipase attenuates Our findings demonstrate acids promote via triglyceride metabolism, suggesting novel droplet-mediated pathway which may be targeted treatment.

Language: Английский

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Pancreatic triglyceride lipase mediates lipotoxic systemic inflammation

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: 130(4), P. 1931 - 1947

Published: Jan. 9, 2020

Visceral adipose tissue plays a critical role in numerous diseases. Although imaging studies often show involvement abdominal diseases, their outcomes may vary from being mild self-limited illness to one with systemic inflammation and organ failure. We therefore compared the pattern of visceral injury during acute pancreatitis diverticulitis determine its Acute pancreatitis–associated had ongoing lipolysis absence adipocyte triglyceride lipase (ATGL). Pancreatic injected into mouse hydrolyzed generated excess nonesterified fatty acids (NEFAs), which caused failure pancreatitis. (PNLIP) increased entered adipocytes by multiple mechanisms, hydrolyzing generating NEFAs. During pancreatitis, obese PNLIP-knockout mice, unlike adipocyte-specific ATGL knockouts, lower lipolysis, milder inflammation, less severe failure, improved survival. were protected adipocyte-induced pancreatic acinar without affecting NEFA signaling or induction. Therefore, diverticulitis, PNLIP leaking can cause excessive independently adipocyte-autonomous ATGL, thereby worsen

Language: Английский

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The mechanism of chlorogenic acid inhibits lipid oxidation: An investigation using multi-spectroscopic methods and molecular docking

Food Chemistry, Journal Year: 2020, Volume and Issue: 333, P. 127528 - 127528

Published: July 9, 2020

Language: Английский

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Lipid Droplets in Cancer

Reviews of physiology, biochemistry and pharmacology, Journal Year: 2020, Volume and Issue: unknown, P. 53 - 86

Published: Jan. 1, 2020

Abstract Lipid droplets have a unique structure among organelles consisting of dense hydrophobic core neutral lipids surrounded by single layer phospholipids decorated with various proteins. Often labeled merely as passive fat storage repositories, they in fact remarkably dynamic life cycle. Being formed within the endoplasmic reticulum membrane, lipid rapidly grow, shrink, traverse cytosol, and engage contacts other to exchange proteins lipids. Their protein composition changes dynamically response cellular states nutrient availability. Remarkably, their biogenesis is induced when cells experience forms nutrient, energy, redox imbalances, including excess complete deprivation. Cancer are continuously exposed oxygen fluctuations capacity switch between alternative acquisition metabolic pathways order strive even during severe stress. supply ensured series uptake scavenging mechanisms, upregulation de novo synthesis, repurposing structural via enzymatic remodeling, or recycling through autophagy. Importantly, most these converge at droplets, which combine different fluxes control usage based on specific needs. It thus not surprising that droplet breakdown an elaborately regulated process occurs complex interplay lipases autophagic degradation. employ ensure energy production balance, modulate autophagy, drive membrane its composition, thereby minimizing stress fostering tumor progression. As regulators (poly)unsaturated fatty acid trafficking, also emerging modulators peroxidation sensitivity ferroptosis. Clearly, dysregulated turnover may be detrimental cancer cells, should provide potential therapeutic opportunities future. In this review, we explore how consolidate trafficking match requirements for cell survival, growth, metastasis.

Language: Английский

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Neutral Lipid Storage Diseases as Cellular Model to Study Lipid Droplet Function

Cells, Journal Year: 2019, Volume and Issue: 8(2), P. 187 - 187

Published: Feb. 21, 2019

Neutral lipid storage disease with myopathy (NLSDM) and ichthyosis (NLSDI) are rare autosomal recessive disorders caused by mutations in the PNPLA2 ABHD5/CGI58 genes, respectively. These genes encode adipose triglyceride lipase (ATGL) α-β hydrolase domain 5 (ABHD5) proteins, which play key roles function of droplets (LDs). LDs, main cellular sites triacylglycerols sterol esters, highly dynamic organelles. Indeed, LDs critical for both metabolism energy homeostasis. Partial or total knockdown is characteristic cells NLSD patients; thus, these natural models one can unravel LD function. In this review we firstly summarize genetic clinical data collected from patients, focusing particularly on muscle, skin, heart, liver damage due to impaired Then, discuss how were used investigate expand current structural functional knowledge LDs.

Language: Английский

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A review on molecular mechanism of alcoholic liver disease

Life Sciences, Journal Year: 2021, Volume and Issue: 274, P. 119328 - 119328

Published: March 10, 2021

Language: Английский

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