Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-021-22397-5
Title: Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity
Authors: Lee, CQE 
Kerouanton, B 
Chothani, S 
Zhang, S 
Chen, Y
Mantri, CK 
Hock, DH
Lim, R 
Nadkarni, R
Huynh, VT
Lim, D
Chew, WL 
Zhong, FL
Stroud, DA
Schafer, S 
Tergaonkar, V 
St John, AL 
Rackham, OJL 
Ho, L 
Keywords: Cell Line
Mitochondria
Humans
Inflammation
Reactive Oxygen Species
Electron Transport Complex IV
Neoplasm Proteins
Nuclear Proteins
MicroRNAs
Up-Regulation
Membrane Potential, Mitochondrial
Gene Knockout Techniques
Genetic Pleiotropy
Primary Cell Culture
Issue Date: 9-Apr-2021
Publisher: Springer Science and Business Media LLC
Citation: Lee, CQE, Kerouanton, B, Chothani, S, Zhang, S, Chen, Y, Mantri, CK, Hock, DH, Lim, R, Nadkarni, R, Huynh, VT, Lim, D, Chew, WL, Zhong, FL, Stroud, DA, Schafer, S, Tergaonkar, V, St John, AL, Rackham, OJL, Ho, L (2021-04-09). Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity. Nature Communications 12 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-021-22397-5
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.
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/191303
ISSN: 20411723
DOI: 10.1038/s41467-021-22397-5
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