期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22397-5
关键词
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资金
- Australian National Health & Medical Research Council (NHMRC) [GNT1140851, GNT1140906]
- A*STAR SSDF fellowship
- A*STAR IAF-PP [H17/01/a0/012]
- European Virus Archive for strain H/PF/2013
- National Research Foundation of Singapore [NRF-NRFF2017-05]
- Howard Hughes Medical Institute International Research Scholar Program [HHMI-IRSP55008732]
- [NRF-CRP17-2017-02]
- [NRF-CRP17-2017-04]
The study identifies a mito-SEP named MOCCI, which can replace NDUFA4 during inflammation to reduce mitochondrial membrane potential and ROS production, providing cell protection and suppressing immune responses. Additionally, the MOCCI transcript generates miR-147b, which enhances antiviral immune responses.
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. Mito-SEPs are small peptides that can modulate oxidative metabolism in mitochondria. Here the authors show that C15ORF48 encodes a mito-SEP, MOCCI, capable of altering mitochondria respiration to suppress inflammation, while C15ORF48 3' untranslated region also contains a miRNA, miR-147b, that synergizes with MOCCI to modulate host anti-viral responses.
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