Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Chen, Fangquan, Kang, Rui, Liu, Jiao, Tang, Daolin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1785063410854002688
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
work_keys_str_mv AT chenfangquan theacsl4networkregulatescelldeathandautophagyindiseases
AT kangrui theacsl4networkregulatescelldeathandautophagyindiseases
AT liujiao theacsl4networkregulatescelldeathandautophagyindiseases
AT tangdaolin theacsl4networkregulatescelldeathandautophagyindiseases
AT chenfangquan acsl4networkregulatescelldeathandautophagyindiseases
AT kangrui acsl4networkregulatescelldeathandautophagyindiseases
AT liujiao acsl4networkregulatescelldeathandautophagyindiseases
AT tangdaolin acsl4networkregulatescelldeathandautophagyindiseases