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

Autor: Daryl Shern Lim, Rhea Nadkarni, Sebastian Schafer, Shan Zhang, Owen J. L. Rackham, Ashley L. St. John, Radiance Lim, Vinh Thang Huynh, Vinay Tergaonkar, Sonia Chothani, David A. Stroud, Daniella H Hock, Baptiste Kerouanton, Lena Ho, Ying Chen, Chinmay K. Mantri, Wei Leong Chew, Franklin L. Zhong, Cheryl Q E Lee
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-22 (2021)
Nature Communications
ISSN: 2041-1723
Popis: 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.
Databáze: OpenAIRE
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