Peroxisomal Protein PEX11β Restores Mitochondrial Function and Behavior in Huntington’s Disease Mice

In a study published in Cell Communication and Signaling, researchers report that PEX11β, a peroxisomal fission protein, is downregulated in Huntington’s and Alzheimer’s disease, and that restoring it in a mouse model of Huntington’s-like pathology alleviated motor and cognitive deficits while reinstating mitochondrial gene expression in the striatum.

Mitochondrial fission and impaired expression and function of respiratory Complex II are established hallmarks of both Huntington’s disease (HD) and Alzheimer’s disease (AD). The authors set out to test whether a shared mechanism might drive mitochondrial fragmentation across these different conditions. Using patient transcriptomic data alongside in vitro cellular models, they connected disease-associated loss of PEX11β to mitochondrial fragmentation and to impaired expression of genes governing mitochondrial fusion and Complex II.

The authors frame this as evidence that PEX11β-mediated regulation of fission-fusion dynamics links mitochondrial integrity to behavioral outcomes.

Both approaches pointed to Yin Yang 1 (YY1) as a critical transcription factor regulating the coordinated expression of PEX11β and Complex II genes. This regulatory link offers a possible explanation for the unique co-expression pattern between PEX11β and respiratory chain complexes that the authors describe in the current study.

The findings also extend toward amyloid-associated neuropathology, the protein-aggregation process central to Alzheimer’s disease, although the abstract indicates this connection is based on analytical insight rather than demonstrated rescue in AD models. Importantly, the in vivo results come from a toxin-induced model of Huntington’s-like pathology, not from patients or from genetic HD models, and the work relies on patient transcriptomic correlations plus cell culture experiments rather than direct measurement in human brain tissue. The article was published on 21 October 2026 as an open-access paper and shared early under a scheme in which the peer-reviewed accepted version is citable but still subject to further edits before the final Version of Record.

Subject of Research: The role of the peroxisomal protein PEX11β in mitochondrial dysfunction and behavioral deficits in Huntington's and Alzheimer's disease models

Article Title: PEX11β-mediated improvement of mitochondrial dysfunction restores behavioral defect and cellular viability in neuropathological conditions

Article References: Kumar, V., Kodam, P., Kunja, C., Balasubramanyam, S. N., Komal, P., Sanyal, A., & Maity, S. (2026). PEX11β-mediated improvement of mitochondrial dysfunction restores behavioral defect and cellular viability in neuropathological conditions. Cell Communication and Signaling. https://doi.org/10.1186/s12964-026-03270-8

Image Credits: AI Generated

DOI: 10.1186/s12964-026-03270-8

Keywords: PEX11β, mitochondrial fission, Huntington's disease, Alzheimer's disease, Complex II, Yin Yang 1, peroxisomes, neurodegeneration, 3-nitropropionic acid, striatum, gene expression, PEX11