Journal article

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

Cheryl QE Lee, Baptiste Kerouanton, Sonia Chothani, Shan Zhang, Ying Chen, Chinmay Kumar Mantri, Daniella Helena Hock, Radiance Lim, Rhea Nadkarni, Thang Huynh Vinh, Daryl Lim, Wei Leong Chew, Franklin L Zhong, David Arthur Stroud, Sebastian Schafer, Vinay Tergaonkar, Ashley L St John, Owen JL Rackham, Lena Ho

NATURE COMMUNICATIONS | NATURE PORTFOLIO | Published : 2021

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. T..

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University of Melbourne Researchers

Grants

Awarded by Australian National Health & Medical Research Council (NHMRC)


Awarded by A*STAR IAF-PP


Awarded by National Research Foundation of Singapore


Awarded by Howard Hughes Medical Institute International Research Scholar Program



Funding Acknowledgements

thank Srikanth Nama for assistance with lentiviral production, Shiqi Lim, Anissa Widjaja, and Eleonora Adami for their technical guidance in Ribo-seq library preparation, Sheryl Beh, Peh Jih Hou, and Liang Chao for technical assistance in RNA-seq, molecular biology, and biochemistry. We thank the Duke-NUS animal facility, FACs facility, the A*STAR/RSC microscopy platform (Graham Wright), and the Bio21 Mass Spectrometry and Proteomics Facility (MMSPF) for their enabling technologies and services. D.A.S. is supported by Australian National Health & Medical Research Council (NHMRC) grants GNT1140851 and GNT1140906. C.Q.E.L. is supported by A*STAR SSDF fellowship. W.L.C. and D.L. acknowledge funding from A*STAR IAF-PP (H17/01/a0/012), V.T. acknowledges support from NRF-CRP17-2017-02. A.L.S. acknowledges funding from NRF-CRP17-2017-04 and thanks the European Virus Archive for strain H/PF/2013. This work is funded by fellowships NRF-NRFF2017-05 (National Research Foundation of Singapore) and HHMI-IRSP55008732 (Howard Hughes Medical Institute International Research Scholar Program) awarded to L.H.