Related Experiment Video
Updated: Nov 9, 2025

In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions
Published on: October 21, 2022
Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity
Cheryl Q E Lee1, Baptiste Kerouanton2, Sonia Chothani2
1Institute of Medical Biology, A*STAR, Singapore, Singapore.
Abstract:
Mito-SEPs are small open reading frame-encoded peptides that localize to the mitochondria to regulate metabolism. Motivated by an intriguing negative association between mito-SEPs and inflammation, here we screen for mito-SEPs that modify inflammatory outcomes and report a mito-SEP named "Modulator of cytochrome C oxidase during Inflammation" (MOCCI) that is upregulated during inflammation and infection to promote host-protective resolution. MOCCI, a paralog of the NDUFA4 subunit of cytochrome C oxidase (Complex IV), replaces NDUFA4 in Complex IV during inflammation to lower mitochondrial membrane potential and reduce ROS production, leading to cyto-protection and dampened immune response. The MOCCI transcript also generates miR-147b, which targets the NDUFA4 mRNA with similar immune dampening effects as MOCCI, but simultaneously enhances RIG-I/MDA-5-mediated viral immunity. Our work uncovers a dual-component pleiotropic regulation of host inflammation and immunity by MOCCI (C15ORF48) for safeguarding the host during infection and inflammation.
Insights
Small open reading frame-encoded peptides (mito-SEPs) regulate inflammation. A novel mito-SEP, MOCCI, protects hosts during inflammation and infection by modulating mitochondrial function and immune responses.
Area of Science:
- Mitochondrial biology
- Immunology
- Molecular genetics
Background:
- Small open reading frame-encoded peptides (mito-SEPs) are emerging regulators of cellular metabolism.
- An inverse correlation between mito-SEPs and inflammation suggests a role in immune modulation.
- Understanding mito-SEP function is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To screen for mito-SEPs that influence inflammatory outcomes.
- To identify and characterize a novel mito-SEP involved in inflammation and immunity.
- To elucidate the molecular mechanisms by which this mito-SEP regulates host defense.
Main Methods:
- Screening of mito-SEPs for their impact on inflammatory pathways.
- Identification and characterization of the "Modulator of cytochrome C oxidase during Inflammation" (MOCCI) mito-SEP.
- Analysis of MOCCI's role in Complex IV function, mitochondrial membrane potential, and ROS production.
- Investigation of MOCCI-generated miR-147b's regulatory effects on NDUFA4 mRNA and innate immune signaling pathways (RIG-I/MDA-5).
Main Results:
- A novel mito-SEP, MOCCI (C15ORF48), was identified and found to be upregulated during inflammation and infection.
- MOCCI replaces NDUFA4 in cytochrome C oxidase (Complex IV), reducing mitochondrial membrane potential and reactive oxygen species (ROS) production.
- This leads to cyto-protection and a dampened immune response.
- MOCCI transcriptionally produces miR-147b, which targets NDUFA4 mRNA, contributing to immune dampening while enhancing RIG-I/MDA-5-mediated viral immunity.
Conclusions:
- MOCCI exhibits dual-component pleiotropic regulation of host inflammation and immunity.
- MOCCI safeguards the host during infection and inflammation through mitochondrial and immune modulation.
- This discovery opens new avenues for understanding and targeting inflammation and immunity.
Related Concept Videos
Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Inflammation
Antigens Involved in Adaptive Immunity
Complete Antigens
Complete antigens possess both immunogenicity and...
Master Transcription Regulators
Cells of the Innate Immune Response
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...

