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X-Linked USP11 Drives Depression-Like Behaviors by Stabilizing CK2α and Disrupting Mitochondrial Function.

Overview

Authors: Yuqi Feng1, Ningyuan Li1, Lingfeng Zhang1, Wei Wang1, Hao Duan1, Siqi Sun1, Ruiling Li1, Yuhui Zhang1, Xinhua Song2, Yingyue Zhang1, Honghan Zhang1, Zhaowen Nie1, Hanchun Yan1, Chao Wang1, Zhongchun Liu1,3,4
ORCID iDs: Lingfeng Zhang, Zhongchun Liu
  1. Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China
  2. Clinical College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, China
  3. Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China
  4. State Key Laboratory of Metabolism and Regulation in Complex Organisms, Wuhan University, Wuhan, China
Institutions: Renmin Hospital of Wuhan University (China); Hubei University of Chinese Medicine (China); Wuhan University (China)
Journal: CNS neuroscience & therapeutics, volume 32, issue 6, article e70934
Dates: received 1 February 2026; accepted 6 May 2026; published online 2 June 2026; in print June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/cns.70934 · PMID 42231570 · PMCID PMC13239159 · OpenAlex W7163317193
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), depression (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Spectral & time-frequency, Evoked potentials, Machine learning
Keywords: casein kinase II subunit alpha (CK2α), depression, mitochondrial dysfunction, mitochondrial fusion and fission, ubiquitination, ubiquitin‐specific peptidase 11 (USP11)
MeSH: Casein Kinase II*, Depression*, Mitochondria*, Animals, Cells, Cultured, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Naphthyridines, Neurons, Prefrontal Cortex (* major topic)
Topic: Ubiquitin and proteasome pathways (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: China Postdoctoral Science Foundation (2025M782239); National Natural Science Foundation of China (82501827, U21A20364)
Citations: not cited yet (Europe PMC); 63 references in the paper

Abstract

Aims: To explore the role and mechanism of X‐linked USP11 in mitochondrial dysfunction associated with depression.

Methods: USP11 knockout mice and USP11 overexpression mice in the prefrontal cortex were constructed, and the role of USP11 in mitochondrial dysfunction in depression was evaluated by behavioral tests and quantitative analysis of mitochondrial function changes in the prefrontal cortex. The interaction protein CK2α of USP11 in depression was identified by IP‐MS, and the role of CK2α was confirmed by using the selective inhibitor CX4945. The direct effects of USP11 and CK2α on mitochondrial function were further verified by using primary neurons.

Results: USP11 mediates depression‐like behaviors and impairs mitochondrial function in mice. Mechanistically, USP11 binds to and deubiquitinates CK2α, stabilizing its protein level and promoting mitochondrial dysfunction. The selective inhibitor CX4945 reverses the impairment of neuronal mitochondrial function by CK2α.

Conclusion: This study demonstrates that USP11 directly binds to and deubiquitinates CK2, affecting mitochondrial function in the mPFC and leading to depressive‐like behaviors in mice.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Data Availability Statement

The data supporting the findings of the study are accessible from the corresponding author upon a reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 6 keywords, 12 MeSH terms, 2 funders, 63 references.

Cite

This paper

Feng, Y., Li, N., Zhang, L., Wang, W., Duan, H., Sun, S., Li, R., Zhang, Y., Song, X., Zhang, Y., Zhang, H., Nie, Z., Yan, H., Wang, C., & Liu, Z. (2026). X-Linked USP11 Drives Depression-Like Behaviors by Stabilizing CK2α and Disrupting Mitochondrial Function. CNS neuroscience & therapeutics, 32(6), e70934. https://doi.org/10.1002/cns.70934

BibTeX

@article{feng2026x,
author = {Feng, Yuqi and Li, Ningyuan and Zhang, Lingfeng and Wang, Wei and Duan, Hao and Sun, Siqi and Li, Ruiling and Zhang, Yuhui and Song, Xinhua and Zhang, Yingyue and Zhang, Honghan and Nie, Zhaowen and Yan, Hanchun and Wang, Chao and Liu, Zhongchun},
title = {{X-Linked USP11 Drives Depression-Like Behaviors by Stabilizing CK2α and Disrupting Mitochondrial Function}},
journal = {CNS neuroscience \& therapeutics},
year = {2026},
month = jun,
volume = {32},
number = {6},
pages = {e70934},
publisher = {Wiley},
issn = {1755-5930},
doi = {10.1002/cns.70934},
url = {https://doi.org/10.1002/cns.70934},
pmid = {42231570},
pmcid = {PMC13239159}
}

RIS

TY - JOUR
AU - Feng, Yuqi
AU - Li, Ningyuan
AU - Zhang, Lingfeng
AU - Wang, Wei
AU - Duan, Hao
AU - Sun, Siqi
AU - Li, Ruiling
AU - Zhang, Yuhui
AU - Song, Xinhua
AU - Zhang, Yingyue
AU - Zhang, Honghan
AU - Nie, Zhaowen
AU - Yan, Hanchun
AU - Wang, Chao
AU - Liu, Zhongchun
TI - X-Linked USP11 Drives Depression-Like Behaviors by Stabilizing CK2α and Disrupting Mitochondrial Function
T2 - CNS neuroscience & therapeutics
J2 - CNS Neurosci Ther
PY - 2026
DA - 2026/06/01
VL - 32
IS - 6
SP - e70934
SN - 1755-5930
PB - Wiley
DO - 10.1002/cns.70934
UR - https://doi.org/10.1002/cns.70934
LA - en
ER -

CSL-JSON

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