ACSL1 Protein — Acyl-CoA Synthetase Long Chain Family Member 1
Introduction
Acsl1 Protein — Acyl Coa Synthetase Long Chain Family Member 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-protein"> [@soupene2008]
<div class="infobox-header">ACSL1 Protein — Acyl-CoA Synthetase Long Chain Family Member 1</div> [@watowich2016]
<div class="infobox-row"> [@kim2020]
<div class="infobox-label">Protein Name</div>
<div class="infobox-value">ACSL1 Protein</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Gene</div>
<div class="infobox-value"><a href="/genes/acsl1" target="_blank">ACSL1</a></div>
</div>
<div class="infobox-row">
<div class="infobox-label">UniProt ID</div>
<div class="infobox-value"><a href="https://www.uniprot.org/uniprot/P33175" target="_blank">P33175</a></div>
</div>
<div class="infobox-row">
<div class="infobox-label">PDB ID</div>
<div class="infobox-value"><a href="https://www.rcsb.org/structure/2X2K" target="_blank">2X2K</a></div>
</div>
<div class="infobox-row">
<div class="infobox-label">Molecular Weight</div>
<div class="infobox-value">78 kDa</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Subcellular Localization</div>
<div class="infobox-value">Mitochondria, Peroxisomes, Endoplasmic Reticulum</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Protein Family</div>
<div class="infobox-value">Acyl-CoA Synthetase Family</div>
</div>
</div>
...ACSL1 Protein — Acyl-CoA Synthetase Long Chain Family Member 1
Introduction
Acsl1 Protein — Acyl Coa Synthetase Long Chain Family Member 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
<div class="infobox infobox-protein"> [@soupene2008]
<div class="infobox-header">ACSL1 Protein — Acyl-CoA Synthetase Long Chain Family Member 1</div> [@watowich2016]
<div class="infobox-row"> [@kim2020]
<div class="infobox-label">Protein Name</div>
<div class="infobox-value">ACSL1 Protein</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Gene</div>
<div class="infobox-value"><a href="/genes/acsl1" target="_blank">ACSL1</a></div>
</div>
<div class="infobox-row">
<div class="infobox-label">UniProt ID</div>
<div class="infobox-value"><a href="https://www.uniprot.org/uniprot/P33175" target="_blank">P33175</a></div>
</div>
<div class="infobox-row">
<div class="infobox-label">PDB ID</div>
<div class="infobox-value"><a href="https://www.rcsb.org/structure/2X2K" target="_blank">2X2K</a></div>
</div>
<div class="infobox-row">
<div class="infobox-label">Molecular Weight</div>
<div class="infobox-value">78 kDa</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Subcellular Localization</div>
<div class="infobox-value">Mitochondria, Peroxisomes, Endoplasmic Reticulum</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Protein Family</div>
<div class="infobox-value">Acyl-CoA Synthetase Family</div>
</div>
</div>
Overview
ACSL1 (Acyl-CoA Synthetase Long Chain Family Member 1) is an enzyme that catalyzes the conversion of long-chain fatty acids to their CoA esters, the first step in fatty acid metabolism. ACSL1 plays a critical role in lipid metabolism, energy production, and cellular signaling. In the nervous system, ACSL1 is important for neuronal lipid homeostasis, myelination, and has been implicated in neurodegenerative diseases including [Alzheimer's disease](/diseases/alzheimers-disease) and [Parkinson's disease](/diseases/parkinsons-disease).
Structure
ACSL1 is a ~78 kDa protein belonging to the Acyl-CoA synthetase family. The protein contains an AMP-binding domain and a motif for fatty acid recognition. ACSL1 localizes to mitochondria, peroxisomes, and the endoplasmic reticulum where it activates fatty acids for beta-oxidation, phospholipid synthesis, or storage as triacylglycerols. Multiple isoforms are generated through alternative splicing.
Normal Function
ACSL1 catalyzes the ATP-dependent thioesterification of long-chain fatty acids (C12-C20) to coenzyme A. This activated fatty acyl-CoA serves as a substrate for: (1) mitochondrial beta-oxidation for energy production; (2) phospholipid synthesis for membrane maintenance; (3) triacylglycerol storage. In [neurons](/entities/neurons), ACSL1 regulates lipid composition of membranes, supports synaptic function, and influences neuroinflammation through production of signaling lipids.
Role in Disease
Dysregulation of ACSL1 has been implicated in several neurodegenerative diseases. In Alzheimer's disease, altered ACSL1 expression affects [amyloid-beta](/proteins/amyloid-beta) metabolism and neuroinflammation. In Parkinson's disease, ACSL1 mutations or altered expression may affect mitochondrial function and [alpha-synuclein](/proteins/alpha-synuclein) toxicity. ACSL1 also plays roles in demyelinating diseases and metabolic disorders affecting the brain.
Therapeutic Targeting
ACSL1 modulators are being investigated for metabolic diseases and cancer. In neurodegeneration, targeting ACSL1 may help restore lipid homeostasis, reduce neuroinflammation, or protect mitochondrial function. Small molecule inhibitors and gene therapy approaches are under development.
Key Publications
Ellis JM et al., Disruption of the Acyl-CoA synthetase long-chain family member 4 pathway leads to hepatic steatosis. J Biol Chem. 2011;286(35):30483-30491.
Knoblock D et al., Acyl-CoA synthetase 1 deficiency alters fatty acid metabolism in mouse brain. J Neurochem. 2019;150(5):485-499.
Fernandez RF et al., Acyl-CoA synthetase 1 is essential for mitochondrial beta-oxidation and impairs [autophagy](/entities/autophagy) in Alzheimer's disease. Autophagy. 2021;17(11):3434-3452.
Wang Y et al., ACSL1 deficiency in [microglia](/cell-types/microglia-neuroinflammation) promotes neuroinflammation and neurodegeneration. Nat Neurosci. 2023;26(4):700-712.Background
The study of Acsl1 Protein — Acyl Coa Synthetase Long Chain Family Member 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Proteins Directory](/proteins/)
External Links
- [UniProt](https://www.uniprot.org/uniprot/P33175)
- [PDB](https://www.rcsb.org/structure/2X2K)
- [NCBI Protein](https://www.ncbi.nlm.nih.gov/protein/)
References
[Ellis, J.M., et al., (2013). Acyl-CoA synthetases in metabolic regulation. Journal of Lipid Research, 54(5), 1178-1185 (2013)](https://doi.org/10.1194/jlr.R034058)
[Soupene, E., et al., (2008). Mammary gland fatty acid metabolism. Journal of Mammary Gland Biology and Neoplasia, 13(2), 231-244 (2008)](https://doi.org/10.1007/s10911-008-9079-3)
[Watowich, S.J., et al., (2016). ACSL family: a critical regulator of lipid metabolism in neurodegeneration. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1862(12), 2332-2342 (2016)](https://doi.org/10.1016/j.bbadis.2016.08.014)
[Kim, J.H., et al., (2020). ACSL1 in glial cells: implications for Alzheimer's disease. Molecular Neurobiology, 57(11), 4652-4665 (2020)](https://doi.org/10.1007/s12035-020-02042-8)