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MOCCI（C15ORF48）的编码和非编码作用协同调节宿主炎症和免疫。

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

机构信息

Institute of Medical Biology, A*STAR, Singapore, Singapore.

Duke-NUS Medical School, Program in Cardiovascular and Metabolic Disorders, Singapore, Singapore.

出版信息

Nat Commun. 2021 Apr 9;12(1):2130. doi: 10.1038/s41467-021-22397-5.

DOI:10.1038/s41467-021-22397-5
PMID:33837217
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8035321/
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.

摘要

线粒体 SEPs 是小开放阅读框编码的肽，定位于线粒体以调节代谢。受线粒体 SEPs 与炎症之间存在有趣的负相关关系的启发，我们在这里筛选了能够改变炎症结果的线粒体 SEPs，并报告了一种名为“炎症期间细胞色素 C 氧化酶调节剂”（MOCCI）的线粒体 SEP，它在炎症和感染期间上调，以促进宿主保护性缓解。MOCCI 是细胞色素 C 氧化酶（复合物 IV）NDUFA4 亚基的同源物，在炎症期间替代复合物 IV 中的 NDUFA4，降低线粒体膜电位并减少 ROS 产生，从而导致细胞保护和免疫反应减弱。MOCCI 转录本还产生 miR-147b，其靶向 NDUFA4 mRNA，具有与 MOCCI 相似的免疫抑制作用，但同时增强 RIG-I/MDA-5 介导的病毒免疫。我们的工作揭示了 MOCCI（C15ORF48）对宿主炎症和免疫的双重多效性调节，以在感染和炎症期间保护宿主。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/e4ee2836984a/41467_2021_22397_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/74a6c7f62388/41467_2021_22397_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/8e457d69ade2/41467_2021_22397_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/3fd52170b3a1/41467_2021_22397_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/fa6650904a1b/41467_2021_22397_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/28663df552a6/41467_2021_22397_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/b473808c10b5/41467_2021_22397_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/5bb5417bb1a0/41467_2021_22397_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/5297ba64c52b/41467_2021_22397_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/e4ee2836984a/41467_2021_22397_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/74a6c7f62388/41467_2021_22397_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/8e457d69ade2/41467_2021_22397_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/3fd52170b3a1/41467_2021_22397_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/fa6650904a1b/41467_2021_22397_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/28663df552a6/41467_2021_22397_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/b473808c10b5/41467_2021_22397_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/5bb5417bb1a0/41467_2021_22397_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/5297ba64c52b/41467_2021_22397_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5bf/8035321/e4ee2836984a/41467_2021_22397_Fig9_HTML.jpg

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