Dataset Information

Switch in Cytochrome C Oxidase Composition Provides Host Protection during Acute Infection

ABSTRACT: Mitochondria play integral roles in the control of inflammation. Mito-SEPs are small open reading frame-encoded peptides that localize to the mitochondria to regulate oxidative metabolism. Motivated by our observation that mito-SEPs are negatively associated with inflammation, we performed a proteo-genomic mito-SEP screen in human aortic endothelial cells to find mito-SEPs that promote resolution of inflammation. Here, we report the discovery of MOCCI (Modulator of Cytochrome C oxidase during Inflammation), an Interleukin-1β-induced mito-SEP encoded by the C15ORF48 gene. MOCCI is a paralog of NADH:Ubiquinone Oxidoreductase Complex Assembly Factor 4 (NDUFA4), the 14th subunit of the mitochondrial respiratory chain Complex IV (CIV). During inflammation, MOCCI displaces NDUFA4 in CIV, aided by repression of NDUFA4 mRNA by a microRNA miR-147b encoded within the 3’ untranslated region of C15ORF48. MOCCI lowers membrane potential and ROS production with overall cyto-protective and anti-inflammatory effects. In parallel, miR-147b exerts a strong anti-viral effect by enhancing RIG-I/MDA-5 pathway of viral recognition and induction of the interferon response. Our findings demonstrate how the coding and non-coding functions of C15ORF48 coordinate to regulate the composition and activity of Complex IV to limit pathogen replication and host inflammation during acute infection. We propose that Complex IV modulation via MOCCI-miR147b is a potential strategy for ameliorating viral-induced hyper-cytokinemia and host immunopathology.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart, Cardiac Muscle Cell

SUBMITTER: David Stroud

LAB HEAD: David Stroud

PROVIDER: PXD024438 | Pride | 2021-03-08

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	200306_Dani_TMT_OTOT_1.raw	Raw
	200306_Dani_TMT_OTOT_10.raw	Raw
	200306_Dani_TMT_OTOT_2.raw	Raw
	200306_Dani_TMT_OTOT_3.raw	Raw
	200306_Dani_TMT_OTOT_4.raw	Raw

Items per page:

1 - 5 of 12

Similar Datasets

Project description:Many small open reading frames (smORFs) embedded in lncRNA transcripts have been shown to encode biologically functional polypeptides (smORFs-encoded polypeptides, SEPs) in different organisms. Despite significant advances in genomics, bioinformatics and proteomics that largely enabled the discovery of novel SEPs, their identification across different biological samples is still hampered by their poor predictability, diminutive size and low relative abundance. Here, we take advantage of NONCODE, a repository containing the most complete collection and annotation of lncRNA transcripts from different species, to build a novel database that attempts to maximize a collection of SEPs from human and mouse lncRNA transcripts. In order to further improve SEP discovery, we implemented two effective and complementary polypeptide enrichment strategies, 30 kDa MWCO filter and C8 SPE column. These combined strategies enabled us to discover 357 and 409 SEPs from, respectively, 8 human cell lines, and 3 mouse cell lines and 8 mouse tissues. Importantly, nineteen of the identified SEPs were then verified through in-vitro expression, immunoblotting, parallel reaction monitoring (PRM) and synthetic peptides. Subsequent bioinformatic analysis revealed that some of the physical and chemical properties of these novel SEPs, including amino acid composition and codon usage, are different from those commonly found in canonical proteins. Intriguingly, nearly 65% of the identified SEPs were found to be initiated with non-AUG start codons. Overall, the strategy presented in this study encompasses an efficient workflow that enabled us to identify 766 novel SEPs across multiple cell lines and tissues, which probably represents the largest number of SEPs detected by mass spectrometry reported to date. These novel SEPs might not only provide new clues for the annotation of noncoding elements in the genome but can also serve as a valuable resource for the functional characterization of individual SEPs.

Dataset Information

Switch in Cytochrome C Oxidase Composition Provides Host Protection during Acute Infection

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets