Very long chain fatty acid-containing lipids: a decade of novel insights from the study of ELOVL4
| Autor: | Richard S. Brush, Gyening Kofi Yeboah, Martin-Paul Agbaga, Ekaterina S. Lobanova |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Thematic Review Series: Seeing 2020: Lipids and Lipid-Soluble Molecules in the Eye Cell signaling RPE retinal pigment epithelium ELOVL elongation of very long-chain fatty acid retinal lipids Very long chain fatty acid QD415-436 030204 cardiovascular system & hematology Biology IS inner segment POS photoreceptor outer segment Synaptic vesicle Neuroprotection Biochemistry SCA34 spinocerebellar ataxia-34 VLC-PUFA very long chain polyunsaturated fatty acid 03 medical and health sciences chemistry.chemical_compound PC phosphatidylcholine 0302 clinical medicine Endocrinology very long chain polyunsaturated fatty acids autosomal dominant Epigenetics AMD age-related macular degeneration Eye Proteins VLC-SFA very long chain saturated fatty acid chemistry.chemical_classification AA arachidonic acid (20:4n6) ERG electroretinography spinocerebellar ataxia 34 Stargardt macular dystrophy erythrokeratodermia variabilis Fatty acid Thematic Review Series Cell Biology Photoreceptor outer segment Cell biology very long chain saturated fatty acids 030104 developmental biology chemistry BBS Bardet-Biedl syndrome STGD3 Stargardt-like macular dystrophy VLC-FA very long chain fatty acid Function (biology) OS outer segment |
| Zdroj: | Journal of Lipid Research, Vol 62, Iss, Pp 100030-(2021) Journal of Lipid Research |
| ISSN: | 0022-2275 |
| Popis: | Lipids play essential roles in maintaining cell structure and function by modulating membrane fluidity and cell signaling. The fatty acid elongase-4 (ELOVL4) protein, expressed in retina, brain, Meibomian glands, skin, testes and sperm, is an essential enzyme that mediates tissue-specific biosynthesis of both VLC-PUFA and VLC-saturated fatty acids (VLC-SFA). These fatty acids play critical roles in maintaining retina and brain function, neuroprotection, skin permeability barrier maintenance, and sperm function, among other important cellular processes. Mutations in ELOVL4 that affect biosynthesis of these fatty acids cause several distinct tissue-specific human disorders that include blindness, age-related cerebellar atrophy and ataxia, skin disorders, early-childhood seizures, mental retardation, and mortality, which underscores the essential roles of ELOVL4 products for life. However, the mechanisms by which one tissue makes VLC-PUFA and another makes VLC-SFA, and how these fatty acids exert their important functional roles in each tissue, remain unknown. This review summarizes research over that last decade that has contributed to our current understanding of the role of ELOVL4 and its products in cellular function. In the retina, VLC-PUFA and their bioactive “Elovanoids” are essential for retinal function. In the brain, VLC-SFA are enriched in synaptic vesicles and mediate neuronal signaling by determining the rate of neurotransmitter release essential for normal neuronal function. These findings point to ELOVL4 and its products as being essential for life. Therefore, mutations and/or age-related epigenetic modifications of fatty acid biosynthetic gene activity that affect VLC-SFA and VLC-PUFA biosynthesis contribute to age-related dysfunction of ELOVL4-expressing tissues. Graphical abstract |
| Databáze: | OpenAIRE |
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