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An international research team has identified a new protein that specifically transports enzymes into peroxisomes. Its mode of action is extraordinary: it operates like a relay racer.
Peroxisomes can be described as tiny vesicles filled with enzymes that are present in all cells, with particularly high concentration in liver cells. They are involved in various important metabolic reactions, including the breakdown of fatty acids and the formation of biomembranes such as the myelin sheath of nerve fibres. They also help to detoxify cells by breaking down harmful hydrogen peroxide.
If peroxisomes do not function properly or are even missing, this can lead to serious consequences, as exemplified by the diseases of the Zellweger spectrum. In these rare hereditary disorders, the functions of the liver, kidneys, brain and other organs are impaired. Individuals affected by the severe form usually live for only a few months.
Although a lot is known about peroxisomes, key questions regarding how exactly they function still remain unanswered. Professor Bettina Warscheid, head of the Chair of Biochemistry II at Julius-Maximilians-Universität (JMU) Würzburg, is working with her team to find answers. Her team, together with partners in the USA and Portugal, has now made new discoveries and published them in the journal Nature Cell Biology.
Protein Acts Like a Relay Racer
Essentially, it is about the way peroxisomes import certain enzymes – without these enzymes, they would not be able to break down fatty acids. Special proteins called peroxins, or PEX for short, are responsible for this process.
‘We have identified a new peroxin, PEX39, which is involved in enzyme import through a previously unknown mechanism,’ says Daniel Wendscheck, first author of the publication and doctoral student in Bettina Warscheid’s team. This discovery is extraordinary because not a single new human peroxin has been described in the last 20 years.
The way PEX39 works can be compared to a relay racer: it grabs the enzymes to be transported, carries them like a baton to the peroxisomes and passes them on to the next racer of the import chain at the peroxisomal membrane.
First Clue From Yeast Cells
Strictly speaking, the PEX39 protein was not a new discovery: its existence has been known since the human genome was decoded. However, until now, no one could say where in the body it is found and what role it plays.
Bettina Warscheid's team discovered this protein, which is present in only extremely small quantities in the body, through mass spectrometric analyses of protein complexes from yeast.
‘Based on this analysis, we found a first indication that it could play a role in peroxisomes,’ says Daniel Wendscheck. The proof finally came with a specially engineered yeast mutant that lacks PEX39: it grew very poorly on oleic acid as carbon source – and in yeast cells, oleic acid is metabolised exclusively in peroxisomes. Many yeast proteins are almost identical to those in humans; studies on human cells then confirmed the importance of PEX39 for the import of peroxisomal enzymes.
Cooperation With Researchers From the USA and Portugal
In addition to Bettina Warscheid's team, the following researchers significantly contributed to this research work: Professor Ralph J. DeBerardinis and Dr Walter W. Chen from the Eugene McDermott Center for Human Growth and Development (USA) and Professor Jorge Azevedo and Dr Tony Rodrigues from the University of Porto (Portugal).
What the Next Research Steps Will Look Like
Bettina Warscheid's group will continue to investigate PEX39. The results could help scientists to better explain disease patterns that have been poorly understood until now.
First of all, however, the Würzburg researchers will focus on exploring the newly discovered functional mechanism of PEX39 in detail at the structural level. ‘Although peroxisomes were discovered 70 years ago, they still hold many mysteries,’ says the JMU professor. ‘Our goal is to solve these mysteries using the latest methods of high-resolution mass spectrometry and structural analysis.’
Prof. Dr. Bettina Warscheid, Chair of Biochemistry II, University of Würzburg, bettina.warscheid@uni-wuerzburg.de, Website: www.biozentrum.uni-wuerzburg.de/biochem2/
PEX39 facilitates the peroxisomal import of PTS2-containing proteins, Nature Cell Biology, 30 July 2025, DOI: 10.1038/s41556-025-01711-z
Like a relay racer: The protein PEX39 (purple) carries enzymes (yellow) like a baton to the peroxiso ...
Source: Daniel Wendscheck
Copyright: University of Wuerzburg
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Like a relay racer: The protein PEX39 (purple) carries enzymes (yellow) like a baton to the peroxiso ...
Source: Daniel Wendscheck
Copyright: University of Wuerzburg
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