Acyl-CoA synthase ACSL4: an essential target in ferroptosis and fatty acid metabolism

Chinese Medical Journal, Journal Year: 2023, Volume and Issue: unknown

Published: July 6, 2023

Long-chain acyl-coenzyme A (CoA) synthase 4 (ACSL4) is an enzyme that esterifies CoA into specific polyunsaturated fatty acids, such as arachidonic acid and adrenic acid. Based on accumulated evidence, the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to execution ferroptosis by triggering phospholipid peroxidation. Ferroptosis a type programmed cell death caused iron-dependent peroxidation lipids; ACSL4 glutathione peroxidase positively negatively regulate ferroptosis, respectively. In addition, essential regulator (FA) metabolism. remodels composition membranes, regulates steroidogenesis, balances eicosanoid biosynthesis. ACSL4-mediated metabolic reprogramming antitumor immunity have attracted much attention in cancer biology. Because it facilitates cross-talk between FA metabolism, also research hotspot diseases ischemia/reperfusion injuries. this review, we focus structure, biological function, unique role ASCL4 various human diseases. Finally, propose might be potential therapeutic target.

Language: Английский

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LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles

Autophagy, Journal Year: 2023, Volume and Issue: 19(11), P. 2837 - 2852

Published: July 20, 2023

LAMP2 (lysosomal associated membrane protein 2) is one of the major components lysosomal membrane. There currently exist three isoforms, LAMP2A, LAMP2B and LAMP2C, they vary in distribution function. LAMP2A serves as a receptor channel for transporting cytosolic proteins process called chaperone-mediated autophagy (CMA). required autophagosome-lysosome fusion cardiomyocytes exosome membranes. LAMP2C primarily implicated novel type which nucleic acids are taken up into lysosomes degradation. In this review, current evidence function each isoform various pathophysiological processes human diseases, well their possible mechanisms, comprehensively summarized. We discuss evolutionary patterns isoforms vertebrates provide technical guidance on investigating these isoforms. also concerned with newly arising questions particular research area that remain unanswered. Advances functions will uncover new links between dysfunction, diseases.Abbreviation: ACSL4: acyl-CoA synthetase long-chain family member 4; AD: Alzheimer disease; Ag: antigens; APP: amyloid beta precursor protein; ATG14: related 14; AVSF: autophagic vacuoles unique sarcolemmal features; BBC3/PUMA: BCL2 binding component 3; CCD: C-terminal coiled coil domain; CMA: autophagy; CVDs: cardiovascular diseases; DDIT4/REDD1: DNA damage inducible transcript ECs: endothelial cells; ER: endoplasmic reticulum; ESCs: embryonic stem GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBA/β-glucocerebrosidase: glucosylceramidase beta; GSCs: glioblastoma HCC: hepatocellular carcinoma; HD: Huntington HSCs: hematopoietic HSPA8/HSC70: heat shock A (Hsp70) 8; IL3: interleukin IR: ischemia-reperfusion; LAMP2: 2; LDs: lipid droplets; LRRK2: leucine rich repeat kinase MA: macroautophagy; MHC: histocompatibility complex; MST1: macrophage stimulating 1; NAFLD: nonalcoholic fatty liver NFE2L2/NRF2: NFE2 like bZIP transcription factor NLRP3: NLR pyrin domain containing PARK7: Parkinsonism deglycase; PD: Parkinson PEA15/PED: proliferation apoptosis adaptor 15; PKM/PKM2: pyruvate M1/2; RA: rheumatoid arthritis; RARA: retinoic acid alpha; RCAN1: regulator calcineurin RCC: renal cell RDA: RNautophagy DNautophagy; RNAi: RNA interference; RND3: Rho Family GTPase SG-NOS3/eNOS: deleterious glutathionylated NOS3; SLE: systemic lupus erythematosus; TAMs: tumor-associated macrophages; TME: tumor microenvironment; UCHL1: ubiquitin hydrolase L1; VAMP8: vesicle 8.

Language: Английский

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International consensus guidelines for the definition, detection, and interpretation of autophagy-dependent ferroptosis

Autophagy, Journal Year: 2024, Volume and Issue: 20(6), P. 1213 - 1246

Published: March 6, 2024

Macroautophagy/autophagy is a complex degradation process with dual role in cell death that influenced by the types are involved and stressors they exposed to. Ferroptosis an iron-dependent oxidative form of characterized unrestricted lipid peroxidation context heterogeneous plastic mechanisms. Recent studies have shed light on involvement specific autophagy (e.g. ferritinophagy, lipophagy, clockophagy) initiating or executing ferroptotic through selective anti-injury proteins organelles. Conversely, other forms reticulophagy lysophagy) enhance cellular defense against damage. Dysregulated autophagy-dependent ferroptosis has implications for diverse range pathological conditions. This review aims to present updated definition ferroptosis, discuss influential substrates receptors, outline experimental methods, propose guidelines interpreting results.

Language: Английский

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Ferroptosis: Mechanisms and role in diabetes mellitus and its complications

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 94, P. 102201 - 102201

Published: Jan. 19, 2024

Language: Английский

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Ferroptosis and pyroptosis are connected through autophagy: a new perspective of overcoming drug resistance

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 17, 2025

Drug resistance is a common challenge in clinical tumor treatment. A reduction drug sensitivity of cells often accompanied by an increase autophagy levels, leading to autophagy-related resistance. The effectiveness combining chemotherapy drugs with inducers/inhibitors has been widely confirmed, but the mechanisms are still unclear. Ferroptosis and pyroptosis can be affected various types autophagy. Therefore, ferroptosis have crosstalk via autophagy, potentially switch cell death under certain conditions. As two forms inflammatory programmed death, different effects on inflammation, cGAS-STING signaling pathway also involved. it plays important role progression some chronic diseases. This review discusses relationship between pyroptosis, attempts uncover reasons behind evasion nature

Language: Английский

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lncRNA ZFAS1 Positively Facilitates Endothelial Ferroptosis via miR-7-5p/ACSL4 Axis in Diabetic Retinopathy

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 17

Published: Aug. 31, 2022

Accumulating evidence has suggested the significant role of long noncoding RNAs (lncRNA) in regulating ferroptosis, while its regulatory mechanism diabetic retinopathy (DR) remains unelucidated. In this work, we first demonstrated that lncRNA zinc finger antisense 1 (ZFAS1) is upregulated high glucose-cultured human retinal endothelial cells (hRECs) and ZFAS1 inhibition attenuated glucose- (HG-) induced which was evidenced by cell viability, total iron ferrous levels, reactive oxygen species (ROS) level, Glutathione Peroxidase 4 (GPX4) expression detection. Mechanistically, validated may act as a competing endogenous RNA competitively binding with microRNA-7-5p (miR-7-5p) modulating downstream molecule acyl-CoA synthetase long-chain family member (ACSL4), now identified classic driver gene ferroptosis process. conclusion, our results demonstrate HG-induced elevation activates hRECs ZFAS1/miR-7-5p/ACSL4 axis serve therapeutic target for dysfunction DR.

Language: Английский

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Chaperone‐mediated autophagy: Molecular mechanisms, biological functions, and diseases

MedComm, Journal Year: 2023, Volume and Issue: 4(5)

Published: Aug. 30, 2023

Chaperone-mediated autophagy (CMA) is a lysosomal degradation pathway that eliminates substrate proteins through heat-shock cognate protein 70 recognition and lysosome-associated membrane type 2A-assisted translocation. It distinct from macroautophagy microautophagy. In recent years, the regulatory mechanisms of CMA have been gradually enriched, including newly discovered NRF2 p38-TFEB signaling, as positive negative pathways CMA, respectively. Normal activity involved in regulation metabolism, aging, immunity, cell cycle, other physiological processes, while dysfunction may be occurrence neurodegenerative disorders, tumors, intestinal atherosclerosis, so on, which provides potential targets for treatment prediction related diseases. This article describes general process its role activities summarizes connection between macroautophagy. addition, human diseases concern or protective are discussed. Our review deepens understanding functions summary past research vision future directions.

Language: Английский

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Stiff Substrate Induces Nucleus Pulposus Cell Ferroptosis via YAP and N‐Cadherin Mediated Mechanotransduction

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(23)

Published: April 6, 2023

Increased tissue stiffness is associated with various pathological processes, such as fibrosis, inflammation, and aging. The matrix of the nucleus pulposus (NP) tissues increases gradually during intervertebral disc degeneration (IDD), while mechanism through which NP cells sense react to remains unclear. In this study, results indicate that ferroptosis involved in stiff substrate-induced cell death. expression acyl-CoA synthetase long-chain family member 4 (ACSL4) group, mediates lipid peroxidation cells. addition, substrate activates hippo signaling cascade induces nuclear translocation yes-associated protein (YAP). Interestingly, inhibition YAP efficient reverse increase ACSL4 caused by stiffness. Furthermore, suppresses N-cadherin overexpression can inhibit via formation N-cadherin/β-catenin/YAP complex, stiffness-induced Finally, effects on IDD progression are further illustrated animal models. These findings reveal a new mechanotransduction cells, providing novel insights into development therapies for treatment IDD.

Language: Английский

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The ACSL4 Network Regulates Cell Death and Autophagy in Diseases

Biology, Journal Year: 2023, Volume and Issue: 12(6), P. 864 - 864

Published: June 15, 2023

Lipid metabolism, cell death, and autophagy are interconnected processes in cells. Dysregulation of lipid metabolism can lead to such as via ferroptosis apoptosis, while lipids also play a crucial role the regulation autophagosome formation. An increased autophagic response not only promotes survival but causes death depending on context, especially when selectively degrading antioxidant proteins or organelles that promote ferroptosis. ACSL4 is an enzyme catalyzes formation long-chain acyl-CoA molecules, which important intermediates biosynthesis various types lipids. found many tissues particularly abundant brain, liver, adipose tissue. linked variety diseases, including cancer, neurodegenerative disorders, cardiovascular disease, acute kidney injury, metabolic disorders (such obesity non-alcoholic fatty liver disease). In this review, we introduce structure, function, ACSL4; discuss its ferroptosis, autophagy; summarize pathological function; explore potential implications targeting treatment diseases.

Language: Английский

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GPX4 degradation contributes to fluoride-induced neuronal ferroptosis and cognitive impairment via mtROS-chaperone-mediated autophagy

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 927, P. 172069 - 172069

Published: April 4, 2024

Language: Английский

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