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Updated: Aug 6, 2026
Mitochondrial Preparation from Microglia for Glycan Analysis
Published on: May 30, 2025
Mitochondrial microprotein MOCCI controls neuroinflammation by altering glial activation states
Kimberle Shen1,2, Ke Guo1, Sze Huey Leong2
1Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (ASTAR), Singapore, Singapore.
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.
Insights
MOCCI, a microprotein, is upregulated in brain inflammation and promotes a neuroprotective glial state. It acts as a brake on neuroinflammation, aiding resolution and showing therapeutic potential for CNS diseases.
Area of Science:
- Neuroscience
- Immunology
- Metabolic regulation
Background:
- Metabolic regulation is key to controlling brain inflammation and glial cell responses.
- MOCCI (C15orf48) is known to regulate gut and lung inflammation.
- MOCCI's role in neuroinflammation was previously unknown.
Purpose of the Study:
- To investigate the role of MOCCI in neuroinflammation.
- To determine MOCCI's effect on glial cell activation and function.
- To explore MOCCI's therapeutic potential in CNS inflammatory diseases.
Main Methods:
- Analysis of MOCCI expression in mouse and human brain samples during inflammation.
- In vitro studies on microglia and astrocyte function with MOCCI deficiency.
- Assessment of MOCCI's role in the cuprizone mouse model of multiple sclerosis.
Main Results:
- MOCCI is upregulated in microglia and astrocytes during brain inflammation.
- MOCCI is essential for proper, beneficial glial activation and promotes a neuroprotective state.
- MOCCI deficiency impairs glial cell migration, phagocytosis, and cytokine secretion.
- MOCCI influences both demyelination and remyelination in a multiple sclerosis model.
Conclusions:
- MOCCI acts as a molecular brake on neuroinflammation.
- MOCCI induction promotes the resolution of inflammation and a neuroprotective glial phenotype.
- MOCCI represents a potential therapeutic target for glial metabolic health and chronic CNS inflammation.
