TY - JOUR
T1 - Coding and non-coding roles of MOCCI (C15ORF48) coordinate to regulate host inflammation and immunity
AU - Lee, Cheryl Q.E.
AU - Kerouanton, Baptiste
AU - Chothani, Sonia
AU - Zhang, Shan
AU - Chen, Ying
AU - Mantri, Chinmay Kumar
AU - Hock, Daniella Helena
AU - Lim, Radiance
AU - Nadkarni, Rhea
AU - Huynh, Vinh Thang
AU - Lim, Daryl
AU - Chew, Wei Leong
AU - Zhong, Franklin L.
AU - Stroud, David Arthur
AU - Schafer, Sebastian
AU - Tergaonkar, Vinay
AU - St John, Ashley L.
AU - Rackham, Owen J.L.
AU - Ho, Lena
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85104107863&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85104107863&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-22397-5
DO - 10.1038/s41467-021-22397-5
M3 - Article
C2 - 33837217
AN - SCOPUS:85104107863
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2130
ER -