Peroxisomal multifunctional protein-2: The enzyme, the patients and the knockout mouse model.
Abstract
The mammalian multifunctional protein-2 (MFP-2, also called multifunctional enzyme 2, D-bifunctional enzyme or 17-beta-estradiol dehydrogenase type IV) was identified by several groups about a decade ago. It plays a central role in peroxisomal beta-oxidation as it handles most, if not all, peroxisomal beta-oxidation substrates. Deficiency of this enzyme in man causes a severe developmental syndrome with abnormalities in several organs but in particular in the brain, leading to death within the first year of life. Accumulation of branched-long-chain fatty acids and very-long-chain fatty acids and a disturbed synthesis of bile acids were documented in these patients. A mouse model with MFP-2 deficiency only partly phenocopies the human disease. Although the expected metabolic abnormalities are present, no neurodevelopmental aberrations are observed. However, the survival of these mice into adulthood allowed to document the importance of this enzyme for the normal functioning of the brain, eyes and testis. In the present review, the identification and biochemical characteristics of MFP-2, and the consequences of MFP-2 dysfunction in humans and in mice will be discussed.
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PEDs directly affecting β-oxidation, such as ACOX1 and MFP2/BP deficiencies, present with neonatal onset and typically lead to death within the first few years of life.
“In contrast, PEDs directly affecting β-oxidation (Figure 1)—such as ACOX1 and MFP2/BP deficiencies—present with neonatal onset and typically lead to death within the first few years of life (Huyghe et al., 2006; Ferdinandusse et al., 2007).”
From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Huyghe et al., 2006
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Self-citationThe neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models
Dawes, M. L., Haberlander, J. P., Islinger, M., & Schrader, M. (2025) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2025.1602343 · Cited by 7 · see citing works
- Authors
- Huyghe, S., Mannaerts, G. P., Baes, M., & Van Veldhoven, P. P.
- Affiliations
- KU Leuven (BE)
- Corresponding author
- Baes, Myriam
- ORCID
- Baes, Myriam
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 1761
- Issue
- 9
- Pages
- 973-994
- ISSN
- 1388-1981 (ISSN-L)
- OpenAlex
- W2092934795
- Cited by
- 91
- References
- 11
- Citations by year
- 2026: 4 · 2025: 4 · 2023: 2 · 2022: 6 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 7 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 5 · 2012: 4
- FWCI
- 0.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- peroxisomal beta-oxidation, peroxisomal disorders, branched-chain fatty acids, very long chain fatty acids, bile acid synthesis, neurodevelopmental abnormalities, knockout mouse models, brain development, testicular development, eye development
- MeSH terms
- Abnormalities, Multiple, Amino Acid Sequence, Animals, Brain, Enoyl-CoA Hydratase, Eye Abnormalities, Fatty Acids, Humans, Male, Models, Molecular, Molecular Sequence Data, Multienzyme Complexes, Organ Specificity, Testis, 17-Hydroxysteroid Dehydrogenases, Mice, Knockout, Peroxisomes, Lipid Metabolism, Mice, Peroxisomal Multifunctional Protein-2
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