Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity
Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity
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.
Lee, Cheryl Q.E.
ad08f275-e403-460b-a5eb-f26e1c9b43b8
Kerouanton, Baptiste
2c117ec2-ce35-4f40-b19a-d5e019de1da7
Chothani, Sonia
24850611-01f3-46ae-af99-8c2693e6ca8f
Rackham, Owen J.L.
8122eb1f-6e9f-4da5-90e1-ce108ccbbcbf
9 April 2021
Lee, Cheryl Q.E.
ad08f275-e403-460b-a5eb-f26e1c9b43b8
Kerouanton, Baptiste
2c117ec2-ce35-4f40-b19a-d5e019de1da7
Chothani, Sonia
24850611-01f3-46ae-af99-8c2693e6ca8f
Rackham, Owen J.L.
8122eb1f-6e9f-4da5-90e1-ce108ccbbcbf
Lee, Cheryl Q.E., Kerouanton, Baptiste and Chothani, Sonia
,
et al.
(2021)
Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity.
Nature Communications, 12, [2130].
(doi: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.
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s41467-021-22397-5
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Accepted/In Press date: 10 March 2021
Published date: 9 April 2021
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Local EPrints ID: 501103
URI: http://eprints.soton.ac.uk/id/eprint/501103
ISSN: 2041-1723
PURE UUID: daafd33a-5955-4a2f-98d4-8ab0b8a10ba4
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Date deposited: 23 May 2025 16:51
Last modified: 22 Aug 2025 02:30
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Author:
Cheryl Q.E. Lee
Author:
Baptiste Kerouanton
Author:
Sonia Chothani
Corporate Author: et al.
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