Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes
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ABSTRACT:
PROVIDER: PRJNA1305433 | ENA |
REPOSITORIES: ENA
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Project description:To understand the mechanism underlying the role of MOTS-c in protecting pancreatic islets from senescence, we performed gene microarray analyses in pancreatic islet cells treated with either MOTS-c or a scrambled peptide
2025-09-11 | GSE305383 | GEO
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: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 mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes
| PRJNA706909 | ENA
Project description:MOTS-c peptide binding protein
| PRJNA1064922 | ENA
Project description:To elucidate the molecular mechanism of MOTS-c against NASH progression, we screened for potential MOTS-c binding proteins using biotin-labeled MOTS-c and HuProt human proteome microarray.
2024-01-18 | GSE253264 | GEO
Project description:LINC00266-1-encoded peptide regulates mRNA splicing
| PRJNA527803 | ENA
Project description:The mRNA transcriptome profiling and splicing profiling mediated by LINC00266-1 and LINC00266-1-encoded peptide were investigated by RNA-seq.
2020-12-21 | GSE128465 | GEO
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. In this study, we found that MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) prevented autoimmune β cell destruction by targeting T cells in non-obese diabetic (NOD) mice. 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-severe combined immunodeficiency (SCID) mice. Metabolic and genomic analyses revealed that MOTS-c modulated T cell phenotype and function by regulating T cell receptor (TCR)/mTOR complex 1 (mTORC1) signaling. Type 1 diabetes (T1D) patients had a lower serum MOTS-c level than did healthy controls. Furthermore, MOTS-c reduced T cell activation by alleviating T cells from the glycolytic stress in T1D patients, suggesting therapeutic potential. Our findings indicate that MOTS-c regulates the T cell phenotype and suppresses autoimmune diabetes.
| S-EPMC10083145 | biostudies-literature