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The ACSL4 Network Regulates Cell Death and Autophagy in Diseases
SIMPLE SUMMARY: ACSL4 is an enzyme involved in the intracellular conversion of long-chain fatty acids and coenzyme A into fatty-acid coenzymes. It plays a vital role in various biological processes, including maintaining cell membrane structure, energy metabolism, and lipid metabolism. Recent studie...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295397/ https://www.ncbi.nlm.nih.gov/pubmed/37372148 http://dx.doi.org/10.3390/biology12060864 |
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author | Chen, Fangquan Kang, Rui Liu, Jiao Tang, Daolin |
author_facet | Chen, Fangquan Kang, Rui Liu, Jiao Tang, Daolin |
author_sort | Chen, Fangquan |
collection | PubMed |
description | SIMPLE SUMMARY: ACSL4 is an enzyme involved in the intracellular conversion of long-chain fatty acids and coenzyme A into fatty-acid coenzymes. It plays a vital role in various biological processes, including maintaining cell membrane structure, energy metabolism, and lipid metabolism. Recent studies have shed light on the involvement of ACSL4 in cell death pathways, autophagy regulation, and the development of human diseases. These findings position ACSL4 as a potential therapeutic target. This review provides an overview of the fundamental structure and mechanisms regulating ACSL4 at both the gene and protein levels, emphasizing its diverse biological functions. Additionally, we discuss the role of ACSL4 in different regulated cell death modalities, including apoptosis and ferroptosis, as well as its involvement in autophagosome formation. Furthermore, we explore potential modulators targeting ACSL4 and emphasize the importance of further research to comprehensively understand the clinical impact of ACSL4 in regulating various pathological conditions. By addressing concerns regarding the systemic impact of therapeutic approaches targeting ACSL4, we aim to pave the way for the development of effective treatments for human diseases. ABSTRACT: Lipid metabolism, cell death, and autophagy are interconnected processes in cells. Dysregulation of lipid metabolism can lead to cell death, such as via ferroptosis and apoptosis, while lipids also play a crucial role in the regulation of autophagosome formation. An increased autophagic response not only promotes cell survival but also causes cell death depending on the context, especially when selectively degrading antioxidant proteins or organelles that promote ferroptosis. ACSL4 is an enzyme that catalyzes the formation of long-chain acyl-CoA molecules, which are important intermediates in the biosynthesis of various types of lipids. ACSL4 is found in many tissues and is particularly abundant in the brain, liver, and adipose tissue. Dysregulation of ACSL4 is linked to a variety of diseases, including cancer, neurodegenerative disorders, cardiovascular disease, acute kidney injury, and metabolic disorders (such as obesity and non-alcoholic fatty liver disease). In this review, we introduce the structure, function, and regulation of ACSL4; discuss its role in apoptosis, ferroptosis, and autophagy; summarize its pathological function; and explore the potential implications of targeting ACSL4 in the treatment of various diseases. |
format | Online Article Text |
id | pubmed-10295397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102953972023-06-28 The ACSL4 Network Regulates Cell Death and Autophagy in Diseases Chen, Fangquan Kang, Rui Liu, Jiao Tang, Daolin Biology (Basel) Review SIMPLE SUMMARY: ACSL4 is an enzyme involved in the intracellular conversion of long-chain fatty acids and coenzyme A into fatty-acid coenzymes. It plays a vital role in various biological processes, including maintaining cell membrane structure, energy metabolism, and lipid metabolism. Recent studies have shed light on the involvement of ACSL4 in cell death pathways, autophagy regulation, and the development of human diseases. These findings position ACSL4 as a potential therapeutic target. This review provides an overview of the fundamental structure and mechanisms regulating ACSL4 at both the gene and protein levels, emphasizing its diverse biological functions. Additionally, we discuss the role of ACSL4 in different regulated cell death modalities, including apoptosis and ferroptosis, as well as its involvement in autophagosome formation. Furthermore, we explore potential modulators targeting ACSL4 and emphasize the importance of further research to comprehensively understand the clinical impact of ACSL4 in regulating various pathological conditions. By addressing concerns regarding the systemic impact of therapeutic approaches targeting ACSL4, we aim to pave the way for the development of effective treatments for human diseases. ABSTRACT: Lipid metabolism, cell death, and autophagy are interconnected processes in cells. Dysregulation of lipid metabolism can lead to cell death, such as via ferroptosis and apoptosis, while lipids also play a crucial role in the regulation of autophagosome formation. An increased autophagic response not only promotes cell survival but also causes cell death depending on the context, especially when selectively degrading antioxidant proteins or organelles that promote ferroptosis. ACSL4 is an enzyme that catalyzes the formation of long-chain acyl-CoA molecules, which are important intermediates in the biosynthesis of various types of lipids. ACSL4 is found in many tissues and is particularly abundant in the brain, liver, and adipose tissue. Dysregulation of ACSL4 is linked to a variety of diseases, including cancer, neurodegenerative disorders, cardiovascular disease, acute kidney injury, and metabolic disorders (such as obesity and non-alcoholic fatty liver disease). In this review, we introduce the structure, function, and regulation of ACSL4; discuss its role in apoptosis, ferroptosis, and autophagy; summarize its pathological function; and explore the potential implications of targeting ACSL4 in the treatment of various diseases. MDPI 2023-06-15 /pmc/articles/PMC10295397/ /pubmed/37372148 http://dx.doi.org/10.3390/biology12060864 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Chen, Fangquan Kang, Rui Liu, Jiao Tang, Daolin The ACSL4 Network Regulates Cell Death and Autophagy in Diseases |
title | The ACSL4 Network Regulates Cell Death and Autophagy in Diseases |
title_full | The ACSL4 Network Regulates Cell Death and Autophagy in Diseases |
title_fullStr | The ACSL4 Network Regulates Cell Death and Autophagy in Diseases |
title_full_unstemmed | The ACSL4 Network Regulates Cell Death and Autophagy in Diseases |
title_short | The ACSL4 Network Regulates Cell Death and Autophagy in Diseases |
title_sort | acsl4 network regulates cell death and autophagy in diseases |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295397/ https://www.ncbi.nlm.nih.gov/pubmed/37372148 http://dx.doi.org/10.3390/biology12060864 |
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