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Cited by 24Lipid metabolism and biosynthesisMetabolism and Genetic DisordersFatty Acid Research and Health

The ELOVL proteins: Very and ultra long-chain fatty acids at the crossroads between metabolic and neurodegenerative disorders.

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Ferrero, Enza, Vaz, Frédéric M., Cheillan, David, Brusco, Alfredo, Marelli, Cecilia·2025·Molecular Genetics and Metabolism
DOI 10.1016/j.ymgme.2025.109050
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Abstract

In lipid metabolism, the fatty acid (FA) elongation system synthesises a wide array of FAs, crucial for various biological functions. The role of this system is to lengthen FA carbon chains to produce FAs with ≥C16, and notably, very long-chain FAs (VLCFAs, C24-C26) and ultra long-chain FAs (ULCFAs, C28 to ≥C36). Elongation occurs in the endoplasmic reticulum (ER) through the actions of a complex of four ER-embedded enzymes, which includes the ELOVL proteins. Together with desaturases that introduce double bonds, these processes significantly increase the variety of FAs. VLCFAs and ULCFAs are required for the biosynthesis of complex lipids, notably glycero(phospho)lipids, ether(phospho)lipids and sphingolipids. The FA elongation system is therefore fundamental for membrane biogenesis and lipid homeostasis, and also for signalling pathways associated with inflammation and cell proliferation. This review focuses on the elongase enzymes, encoded by the ELOVL genes, which catalyze the first and rate-limiting step of the FA elongation cycle. We summarize the physiological roles of the elongase system, with emphasis on the less-characterized ULCFAs, their biological functions, and the functional tools, biomarkers and lipidomic studies used to study them. Additionally, we discuss how ELOVL enzyme defects contribute to disorders at the intersection of metabolic and neurodegenerative conditions, driven by disrupted lipid metabolism and misfolded enzymes in the ER and Golgi.

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  • Organ-specific differences in chain length and number of double bonds in Acbd5-/- mice likely result from the tissue-specific expression of fatty acid elongases and desaturases.

    “These organ-specific differences in chain length and number of double bonds likely result from the tissue-specific expression of fatty acid elongases and desaturases (Ferrero et al., 2025).”

    From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Ferrero et al., 2025

    Section 1.2 (pp. 2–3) describes tissue differences in ELOVL expression and substrate preferences, supporting a possible explanation for organ-specific chain lengths. But it says the mechanism producing tissue-specific degrees of unsaturation is unknown, and it does not establish this explanation for Acbd5-/- mice. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Ferrero, E., Vaz, F. M., Cheillan, D., Brusco, A., & Marelli, C.
Affiliations
  • University of Turin (IT)
  • Amsterdam UMC Location University of Amsterdam (NL)
  • Inserm (FR)
  • Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
Corresponding author
Vaz, Frédéric M.
ORCID
Venue
Molecular Genetics and Metabolism
Publisher
Elsevier BV
Published
2025-03
Volume
144
Issue
3
Pages
109050
ISSN
1096-7192 (ISSN-L)
DOI
10.1016/j.ymgme.2025.109050
OpenAlex
W4407132594
Cited by
24
References
5
Citations by year
2026: 14 · 2025: 10
FWCI
2.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Genetics and Metabolism (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, cc-by-nc-nd)
  • HAL (submittedVersion)
  • Pure Amsterdam UMC (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords
fatty acid elongation, very long chain fatty acids, endoplasmic reticulum, lipid metabolism, neurodegenerative diseases, metabolic disorders, lipidomics, biomarkers, sphingolipid biosynthesis, ether phospholipids, membrane biogenesis, Golgi apparatus
MeSH terms
Fatty Acid Elongases, Acetyltransferases, Animals, Endoplasmic Reticulum, Fatty Acids, Humans, Metabolic Diseases, Neurodegenerative Diseases, Lipid Metabolism

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