REVIEW article

Front. Mol. Neurosci.

Sec. Molecular Signalling and Pathways

Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1603632

This article is part of the Research TopicPeroxisomes and Nervous Tissues: Unraveling Their Physiologic and Pathologic RoleView all 3 articles

Peroxisome dynamics and inter-organelle interactions in neuronal health and disease

Provisionally accepted
  • University of Exeter, Exeter, United Kingdom

The final, formatted version of the article will be published soon.

Peroxisomes are essential organelles, present in all nucleated cells, with key roles in lipid and redox homeostasis. They are important for maintaining healthy cell function, with defects in peroxisome biogenesis and/or metabolism leading to disease. Notably, patients with peroxisomal diseases exhibit predominantly neurological phenotypes, and peroxisomes are observed to be altered in a range of neurodegenerative conditions, highlighting the crucial roles they play in the brain. While most studies so far have focused on the contribution of peroxisomal metabolism, it is becoming apparent that many different aspects of peroxisome biology are necessary for healthy neural function. Peroxisomes are highly dynamic, responding to cellular needs with changes in number, shape and distribution. Furthermore, they do not act in isolation but instead interact and cooperate with a range of organelles to carry out their roles. This review summarizes our current knowledge on the importance of peroxisome dynamics and inter-organelle interactions in neuronal function and dysfunction. It considers their impact on neuronal physiology, and discusses the evidence that defects in these processes are associated with neurological pathophysiology and may thus represent a novel therapeutic target for treating diseases affecting the nervous system. Finally, the review outlines the current knowledge gaps relating to the mechanisms by which peroxisome dynamics and interorganelle interactions influence neuronal (dys)function, proposing potential new research directions to address these and further our understanding of the multi-faceted roles peroxisomes play in brain health and disease.

Keywords: peroxisome, Neuron, membrane dynamics, membrane contact sites, PEX11β, MFF, neurodegeneration

Received: 31 Mar 2025; Accepted: 02 Jun 2025.

Copyright: © 2025 Carmichael. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ruth Ellen Carmichael, University of Exeter, Exeter, United Kingdom

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