Failure to do so results in excessive vascular inflammation that leads to tissue damage in acute settings, and cardiovascular diseases such as atherosclerosis and fibrosis in chronic settings. Our work uncovers a dual-component pleiotropic regulation of host inflammation and immunity by MOCCI (C15ORF48) for safeguarding the host during infection and inflammation.Īctivation of the endothelium by inflammatory triggers initiates a cascade of signaling pathways with the aim of danger signal clearance and resolution of the inflammatory response, ultimately returning the endothelium to its basal state 1. 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. 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.

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. Mito-SEPs are small open reading frame-encoded peptides that localize to the mitochondria to regulate metabolism. Nature Communications volume 12, Article number: 2130 ( 2021)

Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity

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