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

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Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity
Title:
Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity
Other Titles:
Nature Communications
Publication Date:
09 April 2021
Citation:
Lee, C. Q. E., Kerouanton, B., Chothani, S., Zhang, S., Chen, Y., Mantri, C. K., Hock, D. H., Lim, R., Nadkarni, R., Huynh, V. T., Lim, D., Chew, W. L., Zhong, F. L., Stroud, D. A., Schafer, S., Tergaonkar, V., St John, A. L., Rackham, O. J. L., & Ho, L. (2021). Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-22397-5
Abstract:
AbstractMito-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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
This research / project is supported by the National Research Foundation - Competitive Research Programme
Grant Reference no. : NRF-CRP17-2017-02

This research / project is supported by the National Research Foundation - Fellowship Programme
Grant Reference no. : NRF-NRFF2017-05

This research / project is supported by the National Research Foundation - Competitive Research Programme
Grant Reference no. : NRF-CRP17-2017-04

This research / project is supported by the A*STAR - SSDF fellowship
Grant Reference no. : H20SFa0003

This research / project is supported by the A*STAR - IAF-PP
Grant Reference no. : H17/01/ a0/012

Overseas Fundings:- 1) Australian National Health & Medical Research Council (NHMRC) grants GNT1140851 and GNT1140906 2) Howard Hughes Medical Institute International, Research Scholar Program - HHMI-IRSP55008732
Description:
ISSN:
2041-1723