Mitochondrial microprotein MOCCI controls neuroinflammation by altering glial activation states.

Overview

Authors: Kimberle Shen^1,2, Ke Guo¹, Sze Huey Leong², Radiance Lim², Wei Leong Chew^1,3, Cheryl Q E Lee², Lena Ho²

Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (ASTAR), Singapore, Singapore
Cardiovascular Metabolic Disorders Program, Duke-National University of Singapore (NUS) Graduate School, Singapore, Singapore
Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

Institutions: Agency for Science, Technology and Research (Singapore); National University of Singapore (Singapore); Duke-NUS Medical School (Singapore); Genome Institute of Singapore (Singapore)

Journal: Frontiers in immunology, volume 17, article 1798798

Dates: received 29 January 2026; accepted 22 June 2026; published online 9 July 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.3389/fimmu.2026.1798798 · PMID 42495629 · PMCID PMC13391258 · OpenAlex W7167825327

Open access: gold, a free copy (OpenAlex)

Status: data only

Categories: human (organism), mouse (organism), multiple sclerosis (population), cellular / molecular (subfield)

Methods: Statistics, Smoothing, state filtering, decompositions, Physiology & signal measures

Keywords: astrocytes, C15orf48, glia, glia activation, microglia, MOCCI, neuroinflammation

MeSH: Astrocytes*, Microglia*, Mitochondria*, Mitochondrial Proteins*, Neuroglia*, Neuroinflammatory Diseases*, Animals, Brain, Disease Models, Animal, Humans, Mice, Mice, Knockout, Multiple Sclerosis, Phagocytosis (* major topic)

Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex

Citations: not cited yet (Europe PMC); 62 references in the paper

Abstract

Metabolic regulation and its underlying mechanisms play a critical role in controlling and resolving inflammation in the brain, directly shaping glial cell activation and the central nervous system’s response to injury and disease. In our screen for microproteins that modify inflammatory outcomes, we discovered MOCCI (protein product of C15orf48/AA467197) as a significant regulator of gut and lung inflammation. However, its involvement in neuroinflammation is unknown. Here, we show that MOCCI is upregulated in microglia and astrocytes in both the mouse and human brain upon inflammation, and is required for orchestrating proper, complete, and beneficial activation of microglia and astrocytes. Induction of MOCCI triggers the transition of glia into a neuroprotective state and promotes the resolution of inflammation. In vitro, MOCCI deficiency leads to reduced migration, phagocytosis and cytokine secretion in microglia and astrocytes. In the cuprizone mouse model of multiple sclerosis, MOCCI plays a role in both demyelination and remyelination. These results position MOCCI as a molecular brake on neuroinflammation, highlighting its therapeutic potential for targeting glial metabolic health and resolving chronic CNS inflammation in neurodegenerative disease.

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

Code

The paper links to its data, not to its authors' code: see the Data section.

The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

geo:GSE305874 — at NCBI GEO; found in “Data availability statement”
synapse.org/synapse:syn24168322 — at Synapse; found in the text, “MOCCI expression is upregulated upon…”

Data availability statement

The processed single-cell gene expression data generated for this study have been deposited at the Gene Expression Omnibus (GEO) with the accession number GSE305874 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305874) and are publicly available. Gene expression data of the mouse cuprizone model used in this study were downloaded from GSE148676 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE148676) and are publicly available. All R analysis codes used in this study are publicly available as part of the respective R packages cited. Additional information is available upon request.

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

Versions

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 7 authors, 7 keywords, 14 MeSH terms, 62 references.

Cite

This paper

Shen, K., Guo, K., Leong, S. H., Lim, R., Chew, W. L., Lee, C. Q. E., & Ho, L. (2026). Mitochondrial microprotein MOCCI controls neuroinflammation by altering glial activation states. Frontiers in immunology, 17, 1798798. https://doi.org/10.3389/fimmu.2026.1798798

BibTeX

@article{shen2026mitochondrial, author = {Shen, Kimberle and Guo, Ke and Leong, Sze Huey and Lim, Radiance and Chew, Wei Leong and Lee, Cheryl Q E and Ho, Lena}, title = {{Mitochondrial microprotein MOCCI controls neuroinflammation by altering glial activation states}}, journal = {Frontiers in immunology}, year = {2026}, month = jul, volume = {17}, pages = {1798798}, publisher = {Frontiers Media SA}, issn = {1664-3224}, doi = {10.3389/fimmu.2026.1798798}, url = {https://doi.org/10.3389/fimmu.2026.1798798}, pmid = {42495629}, pmcid = {PMC13391258} }

RIS

TY - JOUR AU - Shen, Kimberle AU - Guo, Ke AU - Leong, Sze Huey AU - Lim, Radiance AU - Chew, Wei Leong AU - Lee, Cheryl Q E AU - Ho, Lena TI - Mitochondrial microprotein MOCCI controls neuroinflammation by altering glial activation states T2 - Frontiers in immunology J2 - Front Immunol PY - 2026 DA - 2026/07/09 VL - 17 SP - 1798798 SN - 1664-3224 PB - Frontiers Media SA DO - 10.3389/fimmu.2026.1798798 UR - https://doi.org/10.3389/fimmu.2026.1798798 LA - en ER -

CSL-JSON

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