The physiological functions of human peroxisomes
Open accessAbstract
Peroxisomes are subcellular organelles that play a central role in human physiology by catalyzing a range of unique metabolic functions. The importance of peroxisomes for human health is exemplified by the existence of a group of usually severe diseases caused by an impairment in one or more peroxisomal functions. Among others these include the Zellweger spectrum disorders, X-linked adrenoleukodystrophy, and Refsum disease. To fulfill their role in metabolism, peroxisomes require continued interaction with other subcellular organelles including lipid droplets, lysosomes, the endoplasmic reticulum, and mitochondria. In recent years it has become clear that the metabolic alliance between peroxisomes and other organelles requires the active participation of tethering proteins to bring the organelles physically closer together, thereby achieving efficient transfer of metabolites. This review intends to describe the current state of knowledge about the metabolic role of peroxisomes in humans, with particular emphasis on the metabolic partnership between peroxisomes and other organelles and the consequences of genetic defects in these processes. We also describe the biogenesis of peroxisomes and the consequences of the multiple genetic defects therein. In addition, we discuss the functional role of peroxisomes in different organs and tissues and include relevant information derived from model systems, notably peroxisomal mouse models. Finally, we pay particular attention to a hitherto underrated role of peroxisomes in viral infections.
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ALDP transport involves cooperative binding of two VLCFAcyl-CoAs, ATP binding, and ALDP homodimerization, followed by outward-facing conformational change allowing release of VLCFAcylCoA into the peroxisome matrix, where VLCFAcyl-CoA undergoes peroxisomal β-oxidation.
“Transport involves cooperative binding of two VLCFAcyl-CoAs, ATP binding, and ALDP homodimerization [147], followed by outward-facing ALDP conformational change allowing for the release of VLCFAcylCoA into the peroxisome matrix [148], where VLCFAcyl-CoA undergoes peroxisomal β-oxidation [149].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [149]
Peroxisomal β-oxidation of VLCFAs has a unique degradative function.
“Peroxisomal β-oxidation of VLCFAs has a unique degradative function [149].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [149]
Allowing ABCD1 expression to be reinstalled in OL peroxisomes is likely to restore the function of crucial metabolic pathways.
“Based on the surprisingly rapid vector effect, we postulated that the axonopathy of these mice was largely functional [176]; indeed, allowing ABCD1 expression to be reinstalled in OL peroxisomes is likely to restore the function of crucial metabolic pathways [149].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [149]
DHA synthesis requires three consecutive rounds of elongation and desaturation at the ER followed by a single, final chain-shortening step by peroxisomal β-oxidation.
“Originating from linolenic acid, the synthesis of DHA requires three consecutive rounds of elongation and desaturation at the ER followed by a single, final chain-shortening step by peroxisomal β-oxidation (Wanders et al., 2023).”
From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Wanders et al., 2023
Ether lipid synthesis requires the cooperation of peroxisomes and the ER.
“Ether lipid synthesis requires the cooperation of peroxisomes and the ER (Wanders et al., 2023).”
From The neurological pathology of peroxisomal ACBD5 deficiency – lessons from patients and mouse models (2025) · cites this paper as Wanders et al., 2023
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- Authors
- Wanders, R. J. A., Baes, M., Ribeiro, D., Ferdinandusse, S., & Waterham, H. R.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- KU Leuven (BE)
- University of Aveiro (PT)
- Corresponding author
- Wanders, Ronald J. A.
- Waterham, Hans R.
- Venue
- Physiological Reviews
- Publisher
- American Physiological Society
- Published
- 2023-01-01
- Volume
- 103
- Issue
- 1
- Pages
- 957-1024
- ISSN
- 0031-9333 (ISSN-L)
- 1522-1210
- OpenAlex
- W4291020935
- Cited by
- 228
- References
- 44
- Citations by year
- 2026: 57 · 2025: 83 · 2024: 59 · 2023: 28 · 2022: 1
- FWCI
- 5.29
- Type
- journal article
- Language
- en
- Open access
- green
- lirias.kuleuven.be
- Licence
- other-oa
- Locations
- Physiological Reviews (publishedVersion)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Funders
- Stichting Metakids
- European Commission
- ZonMw
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- KU Leuven
- Hersenstichting
- Vlaamse regering
- Fundação para a Ciência e a Tecnologia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- peroxisomes, peroxisomal metabolism, peroxisome biogenesis, Zellweger spectrum disorder, X-linked adrenoleukodystrophy, Refsum disease, lipid droplets, lysosomes, endoplasmic reticulum, mitochondria, peroxisome dysfunction
- MeSH terms
- Animals, Humans, Peroxisomes, Mice
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