Peroxisome Biogenesis and Function in Metabolic Disorders

Peroxisomes are versatile membrane-bound organelles pivotal to cellular lipid metabolism, reactive oxygen species homeostasis, and the assembly of specialised lipids such as ether glycerophospholipids. Their biogenesis is orchestrated by peroxin (PEX) proteins that govern peroxisome membrane formation, matrix protein import and proliferation. Impairment of peroxisome formation or function leads to a spectrum of inherited metabolic conditions collectively termed peroxisome biogenesis disorders, characterised by the accumulation of very long chain fatty acids and deficits in plasmalogens. These deficits underlie neurological dysfunction, hepatic abnormalities and developmental delays. Within the peroxisomal lumen, enzymes catalyse β-oxidation of specific fatty acids, synthesis of bile acid intermediates and detoxification of hydrogen peroxide. Peroxisomes also engage in dynamic cross-talk with mitochondria and the endoplasmic reticulum, ensuring coordination of lipid flux, redox balance and metabolic signalling. A growing body of research has illuminated the molecular choreography of peroxisome assembly, the selectivity of protein import mechanisms and the adaptive responses that buffer metabolic stress. Advances in imaging and biochemical assays have refined our understanding of peroxisomal dynamics in health and disease, opening avenues for diagnostic and therapeutic innovation in metabolic disorders.

Research from Nature Portfolio

Recent studies have introduced novel live-cell imaging reagents that specifically stain functional and dysfunctional peroxisomes, addressing a longstanding gap in peroxisomal diagnostics. By engineering fatty acid–conjugated BODIPY probes and refining them into red and far-red fluorescent PeroxiSPY compounds, researchers have achieved bright, non-cytotoxic, peroxisome-specific labelling in a range of mammalian models. These tools facilitate high-resolution visualisation of peroxisome dynamics and enable the rapid detection of biogenesis defects in patient-derived cell lines. In parallel, mechanistic work has delineated the import cycle of proteins bearing an amino-terminal targeting sequence. A comprehensive model now describes how PTS2 cargo, escorted by the adaptor PEX7, traverses the peroxisomal membrane via a tyrosine–glycine-rich conduit and is recycled through discrete retrotranslocation steps mediated by PEX39. Together, these advances elucidate fundamental processes of peroxisome assembly and furnish new strategies for probing peroxisomal function in metabolic disease contexts.

Peroxisome Biogenesis and Function in Metabolic Disorders publication trend

The graph below shows the total number of articles in peroxisome biogenesis and function in metabolic disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Peroxisome: A membrane-bound organelle involved in lipid metabolism and detoxification of reactive oxygen species.

Peroxisome biogenesis disorder: A group of inherited conditions caused by defects in proteins required for peroxisome assembly, leading to metabolic dysfunction.

Protein targeting signal 1 (PTS1): A carboxy-terminal amino acid sequence that directs proteins into the peroxisomal matrix via the PEX5 receptor.

Protein targeting signal 2 (PTS2): An amino-terminal sequence recognised by the PEX7 receptor to mediate import of specific peroxisomal enzymes.

β-oxidation: The stepwise enzymatic breakdown of fatty acids within peroxisomes or mitochondria to generate acetyl-CoA.

Reactive oxygen species: Chemically reactive molecules containing oxygen that can cause oxidative damage but also serve signalling roles.

References

1. Fluorescent fatty acid conjugates for live cell imaging of peroxisomes. Nature Communications (2024).
2. Import mechanism of peroxisomal proteins with an N-terminal signal sequence. Nature Cell Biology (2025).
3. Towards solving the mystery of peroxisomal matrix protein import. Trends in Cell Biology (2023).
4. Glutathione and peroxisome redox homeostasis. Redox Biology (2023).
5. Structural and functional roles of ether lipids. Protein & Cell (2017).
6. Metabolic Interplay between Peroxisomes and Other Subcellular Organelles Including Mitochondria and the Endoplasmic Reticulum. Frontiers in Cell and Developmental Biology (2016).
7. Biochemistry and genetics of inherited disorders of peroxisomal fatty acid metabolism[S]. Journal of Lipid Research (2010).
8. Zellweger spectrum disorders: clinical overview and management approach. Orphanet Journal of Rare Diseases (2015).
9. Peroxisomal Hydrogen Peroxide Metabolism and Signaling in Health and Disease. International Journal of Molecular Sciences (2019).