Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA272824 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Mitochondria are known to be functional organelles, but their role as a signaling unit is increasingly being appreciated. The recent identification of a short open reading frame (sORF) in the mitochondrial DNA (mtDNA) that encodes a signaling peptide, humanin, suggests the possible existence of additional sORFs in the mtDNA that yield bioactive peptides. Here we report the identification of a sORF within the mitochondrial 12S rRNA encoding a 16-amino-acid peptide named MOTS-c (mitochondrial open-reading-frame of the twelve S rRNA -c) that regulates insulin sensitivity and metabolic homeostasis. MOTS-c is detected in various tissues and in circulation in an age-dependent manner. Its primary target organ appears to be the skeletal muscle and its cellular actions inhibit the folate cycle and its tethered de novo purine biosynthesis, causing a significant accumulation of AICAR levels concomitantly with AMPK activation. MOTS-c treatment in mice prevented age-dependent and high-fat diet-induced insulin resistance, as well as diet-induced obesity. These results suggest that mitochondria may be more actively engaged in regulating metabolic homeostasis than previously recognized, through the production of peptides encoded within its genome that act at the cellular and organismal level. Human embryonic kidney cells (HEK293 cell line) were cultured in 10-cm dishes in 7 mL of phenol-free DMEM supplemented with 10% FBS and incubated with water (controls) or the 16-amino-acid peptide mitochondrial open-reading-frame of the twelve S rRNA-c (MOTS-c, 10 uM) for 4 or 72 hours prior to RNA extraction.
2015-03-07 | E-GEOD-65068 | biostudies-arrayexpress
Project description:Mitochondria are known to be functional organelles, but their role as a signaling unit is increasingly being appreciated. The recent identification of a short open reading frame (sORF) in the mitochondrial DNA (mtDNA) that encodes a signaling peptide, humanin, suggests the possible existence of additional sORFs in the mtDNA that yield bioactive peptides. Here we report the identification of a sORF within the mitochondrial 12S rRNA encoding a 16-amino-acid peptide named MOTS-c (mitochondrial open-reading-frame of the twelve S rRNA -c) that regulates insulin sensitivity and metabolic homeostasis. MOTS-c is detected in various tissues and in circulation in an age-dependent manner. Its primary target organ appears to be the skeletal muscle and its cellular actions inhibit the folate cycle and its tethered de novo purine biosynthesis, causing a significant accumulation of AICAR levels concomitantly with AMPK activation. MOTS-c treatment in mice prevented age-dependent and high-fat diet-induced insulin resistance, as well as diet-induced obesity. These results suggest that mitochondria may be more actively engaged in regulating metabolic homeostasis than previously recognized, through the production of peptides encoded within its genome that act at the cellular and organismal level.
2015-03-07 | GSE65068 | GEO
Project description:The emergence of small open reading frame (sORF)-encoded peptides (SEPs) is rapidly expanding the known proteome at the lower end of the size distribution. Here, we show that the mitochondrial proteome is enriched for proteins smaller than 100 a.a. (defined as SEPs). Using a prediction and validation pipeline for small open-reading-frame (sORF)-encoded peptides (SEPs), we report the discovery of 16 endogenous nuclear encoded, mitochondrial-localized SEPs (mito-SEPs). Through functional prediction, proteomics, metabolomics and metabolic flux modeling, we demonstrate that BRAWNIN (BR), a 71 amino acid peptide encoded by the C12orf73 gene, is essential for respiratory chain complex III (CIII) assembly. In human cells, BR is induced by the energy-sensing AMPK pathway, and its depletion impairs mitochondrial ATP production. In vivo, BR is enriched in muscle tissues and its maternal zygotic deletion in zebrafish causes complete CIII loss, resulting in severe growth retardation, lactic acidosis and early death. Our findings demonstrate that BR is essential for oxidative phosphorylation across vertebrate species. We propose that mito-SEPs are an untapped resource for essential regulators of oxidative metabolism. The dataset included in this entry is for the Zebrafish and MEF BR knockouts.
2020-03-18 | PXD016718 | Pride
Project description:Mitochondria are important organelles controlling productivity and metabolism in cells. Recent studies have found that there are short open reading frames on mitochondrial genomes that has not been discovered before, which could encode short peptides, and we called them mitochondrial-derived peptides (MDPs), including MOTS-c encoded by 12S-rRNA, Humanin(HN) and SHLP1-6 encoded by 16S-rRNA. As a new class of circulating signaling molecules, these mitochondrial-derived peptides play an important function in certain human life activities or the occurrence of diseases. In order to study the potential unknown function of MDP and the molecular mechanism behind it, overexpressing MDPs were used as bait protein to conduct systematic immunoprecipitation experiment.
2022-01-12 | PXD030898 |
Project description:A large number of lncRNAs has been found aberrant expression in breast cancer and paly functional role in tumor progression. However, the role of small peptide hidden in lncRNA are largely unexplored. In this study, we applied the CRISPR/Cas9 screen and ribosome profiling to systematically discover nocanonical open reading frame encoded in long noncoding RNAs (lncRNAs) and explored their critical roles in ER+ breast cancer.
2023-03-18 | GSE196927 | GEO
Project description:Synthesis of the metabolic transcription factor C/EBPβ-LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the C/EBPβ-mRNA. We tested if that reduced C/EBPβ-LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice.
2019-01-16 | E-MTAB-6435 | biostudies-arrayexpress
Project description:Mitochondria are principal metabolic organelles that are increasingly unveiled as immune regulators. However, it is currently not known whether mitochondrial-encoded peptides modulate T cells to induce changes in phenotype and function. Here, we found that MOTS-c prevented autoimmune β-cell destruction via phenotypical and functional changes of T cells in NOD mice, a type 1 diabetes (T1D) animal model. MOTS-c ameliorated the development of hyperglycemia and reduced islet-infiltrating immune cells. Furthermore, adoptive transfer of T cells from MOTS-c-treated NOD mice significantly decreased the incidence of diabetes in NOD-SCID mice. Metabolic and genomic analysis revealed that MOTS-c modulated T cell phenotype and function by regulating TCR/mTORC1 pathway. We observed that T1D patients had a lower serum MOTS-c level than healthy controls. Furthermore, MOTS-c reduced T cell activation by alleviating T cells from the glycolytic stress in T1D patients suggesting a potential therapeutic implication. Our findings indicate that the MOTS-c acts as a regulator of T cell phenotype and function in autoimmune diabetes.
2021-03-06 | GSE168324 | GEO
Project description:Proteome isolated from C57BL/6J mouse B and T cells are evluated for the presence of novel open reading frame products (nORFs). Translation products encoded by non canonical or novel open reading frame (ORF) genomic regions are generally considered too small to play any significant biological role, and dismissed as inconsequential. We conduct a systematic study of novel ORFs to gain new insights into normal biological and disease processes.
2021-09-09 | PXD022099 | Pride
Project description:Recent technological advances have expanded the annotated protein coding content of mammalian genomes, as hundreds of previously unidentified, short open reading frame (ORF)-encoded peptides (SEPs) have now been found to be translated. Although several studies have identified important physiological roles for this emerging protein class, a general method to define their interactomes is lacking. Here, we demonstrate that genetic incorporation of the photo-crosslinking noncanonical amino acid AbK into SEP transgenes allows for the facile identification of SEP cellular interaction partners using affinity-based methods. From a survey of seven SEPs, we report the discovery of short ORF-encoded histone binding protein (SEHBP), a conserved microprotein that interacts with chromatin-associated proteins, localizes to discrete genomic loci, and induces a robust transcriptional program when overexpressed in human cells. This work affords a straightforward method to help define the physiological roles of SEPs and demonstrates its utility by identifying SEHBP as a short ORF-encoded transcription factor.
2021-01-11 | GSE164239 | GEO
