Five acyl-CoA synthetase long-chain family members (ACSLs) are responsible for catalyzing diverse long-chain fatty acids (LCFAs) into LCFA-acyl-coenzyme A (CoA) for their subsequent metabolism, including fatty acid oxidation (FAO), lipid synthesis, and protein acylation. In this review, we focus on ACSLs and their LCFA substrates and introduce their involvement in regulation of cancer proliferation, metastasis, and therapeutic resistance. Along with the recognition of the decisive role of ACSL4 in ferroptosis - an immunogenic cell death (ICD) initiated by lipid peroxidation - we review the functions of ACSLs on regulating ferroptosis sensitivity. Last, we discuss the current understanding of ACSL on the antitumor immune response. We emphasize the necessity to explore the functions of immune cells expressing ACSLs for developing novel strategies to augment immunotherapy by targeting ACSL.
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http://dx.doi.org/10.1016/j.tem.2024.09.003 | DOI Listing |
Mol Oncol
January 2025
Center for Molecular Medicine, MaineHealth Institute for Research, Scarborough, ME, USA.
Multiple myeloma (MM) is an incurable cancer of plasma cells with a 5-year survival rate of 59%. Dysregulation of fatty acid (FA) metabolism is associated with MM development and progression; however, the underlying mechanisms remain unclear. Herein, we explore the roles of long-chain fatty acid coenzyme A ligase (ACSL) family members in MM.
View Article and Find Full Text PDFGeroscience
November 2024
Department of Neurology, Louisiana State University Health, LSU Health Sciences Center Shreveport, 1501 Kings Hwy, Shreveport, LA, 71103-3932, USA.
Alzheimer's disease (AD), the leading cause of dementia, affects over 55 million people worldwide and is often accompanied by depression and anxiety. Both significantly impact patients' quality of life and impose substantial societal and economic burdens on healthcare systems. Identifying the complex regulatory mechanisms that contribute to the psychological and emotional deficits in AD will provide promising therapeutic targets.
View Article and Find Full Text PDFTrends Endocrinol Metab
October 2024
Department of Immunology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China; Cell Architecture Research Institute, Huazhong University of Science and Technology, Wuhan, China. Electronic address:
Five acyl-CoA synthetase long-chain family members (ACSLs) are responsible for catalyzing diverse long-chain fatty acids (LCFAs) into LCFA-acyl-coenzyme A (CoA) for their subsequent metabolism, including fatty acid oxidation (FAO), lipid synthesis, and protein acylation. In this review, we focus on ACSLs and their LCFA substrates and introduce their involvement in regulation of cancer proliferation, metastasis, and therapeutic resistance. Along with the recognition of the decisive role of ACSL4 in ferroptosis - an immunogenic cell death (ICD) initiated by lipid peroxidation - we review the functions of ACSLs on regulating ferroptosis sensitivity.
View Article and Find Full Text PDFCell Biochem Funct
September 2024
Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Pilani, Rajasthan, India.
Long-chain acyl-CoA synthetases (ACSLs) are pivotal enzymes in fatty acid metabolism, essential for maintaining cellular homeostasis and energy production. Recent research has uncovered their significant involvement in the pathophysiology of various kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), and renal cell carcinoma (RCC). While ACSL1, ACSL3, ACSL4, and ACSL5 have been extensively studied for their roles in processes such as ferroptosis, lipid peroxidation, renal fibrosis, epithelial-mesenchymal transition, and tumor progression, the role of ACSL6 in kidney diseases remain largely unexplored.
View Article and Find Full Text PDFInt J Mol Sci
June 2023
Department of Forensic Medicine, School of Basic Medicine and Biological Sciences, Soochow University, Suzhou 215123, China.
As an iron-dependent regulated form of cell death, ferroptosis is characterized by iron-dependent lipid peroxidation and has been implicated in the occurrence and development of various diseases, including nervous system diseases and injuries. Ferroptosis has become a potential target for intervention in these diseases or injuries in relevant preclinical models. As a member of the Acyl-CoA synthetase long-chain family (ACSLs) that can convert saturated and unsaturated fatty acids, Acyl-CoA synthetase long-chain familymember4 (ACSL4) is involved in the regulation of arachidonic acid and eicosapentaenoic acid, thus leading to ferroptosis.
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