Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.
-
The 51-bp ORF lies within the mitochondrial 12S rRNA and cannot be translated by the mitochondrial ribosome, so the peptide must be made in the cytosol from an exported mitochondrial transcript.
"MOTS-c peptide translation obligatorily occurs in the cytoplasm using the standard genetic code because mitochondrial translation, using the mitochondria-specific genetic code, yields tandem start and stop codons"
-
Nuclear NUMT copies of the locus do not encode a peptide identical to mitochondrially encoded MOTS-c.
"we found that none of the putative NUMT-derived peptides shared complete homology with mitochondrial encoded MOTS-c"
-
The endogenous peptide circulates in human and rodent plasma.
"as well as in circulation in human and rodent plasma as determined with a MOTS-c specific ELISA"
-
MOTS-c blocks the folate cycle and de novo purine biosynthesis, causing AICAR to accumulate and AMPK to be phosphorylated.
"resulting in an accumulation of endogenous AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) to levels higher than 20-fold in MOTS-c-ST cells compared to control cells"
MOTS-c peptide increases survival and decreases bacterial load in mice infected with MRSA.
-
MOTS-c improves survival and lowers bacterial load in MRSA-challenged mice and enhances macrophage bactericidal capacity.
"we demonstrated that a Mitochondria-derived peptide (MOTS-c) could significantly improve the survival rate and decrease bacteria loads in MRSA-challenged mice"
The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress.
-
MOTS-c binds ARE-containing promoter DNA directly in vitro and occupies the HO-1 and NQO1 promoters in stressed cells.
"we found that MOTS-c directly bound DNA sequences of ARE-containing promoter regions of NRF2 target genes, including HO-1, NQO1, UGT1A1, UGT1A6, TXN, FTL, and GPX2, in a concentration-dependent manner"
-
The NFE2L2/NRF2 interaction is nuclear and stress-inducible, and the two proteins enter the nucleus independently.
"NRF2 co-immunoprecipitated with MOTS-c only from nuclear extracts of cells treated with GR and tBHP for 3 hr"
-
MOTS-c also associates with ATF1, with the interaction strengthened by glucose restriction.
"We found that MOTS-c co-immunoprecipitated with ATF1 in the nucleus and that their interaction was strengthened after GR (3 hr)"
-
Endogenous peptide is detectable in the nucleus at rest, and nuclear entry requires the hydrophobic core.
"to alanines (8YIFY11 to 8AAAA11) prevented EGFP-MOTS-c from entering the nucleus"
MOTS-c improves osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via TGF-β/Smad pathway.
-
Synthetic MOTS-c promotes osteogenic differentiation of rat bone-marrow mesenchymal stem cells, reversed by TGF-beta1 knockdown.
"MOTS-c treatment could remarkably stimulate the formation of calcified nodules in BMSCs."
MOTS-c improves osteoporosis by promoting the synthesis of type I collagen in osteoblasts via TGF-β/SMAD signaling pathway.
-
Micromolar synthetic MOTS-c increased hFOB1.19 viability and COL1A1/COL1A2 expression, partially reversed by TGF-beta or SMAD7 knockdown.
"Cell viability was significantly increased after treatment of 1.0 μM MOTS-c for 24 h or 0.5 μM MOTS-c for 48 h in a time-dependent manner."
Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition.
-
MOTS-c is detectable in human skeletal muscle and plasma, with muscle levels rising and circulating levels falling with age.
"Circulating MOTS-c reduced with age, but older (70-81 y) and middle-aged (45-55 y) men had ~1.5-fold higher skeletal muscle MOTS-c expression than young (18-30 y)."
-
In human skeletal muscle, MOTS-c expression was not associated with antioxidant response element-related gene expression, in contrast to the ARE/NRF2 mechanism reported in cultured cells.
"expression is not associated with antioxidant response element (ARE)-related genes as previously seen in culture"
A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c.
-
The Asian-specific m.1382A>C variant causes a K14Q substitution in MOTS-c and is associated with type 2 diabetes in men; K14Q peptide has reduced insulin-sensitising activity.
"Here, we showed an Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide."
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.
-
Exercise induces endogenous MOTS-c expression in human skeletal muscle and in the circulation.
"Western blotting for endogenous MOTS-c in skeletal muscle revealed that relative levels (i.e. individual changes based on pre-exercise values) significantly increased after exercise (11.9-fold)"
-
Exogenously applied labelled peptide enters the nucleus in a time-dependent manner.
"Using fluorescently labeled MOTS-c peptide (MOTS-c-FITC), we confirmed that exogenously treated MOTS-c also dynamically translocated to the nucleus in a time-dependent manner"
-
The protective effect of MOTS-c against glucose restriction and serum deprivation in myoblasts requires HSF1.
"siRNA-mediated HSF1 knockdown reversed the protective effects of MOTS-c against GR/SD in myoblasts"
MOTS-c reduces myostatin and muscle atrophy signaling.
-
MOTS-c raises AKT Ser473 (but not Thr308) phosphorylation and increases CK2 substrate phosphorylation in skeletal muscle of diet-induced obese mice.
"MOTS-c elevated the phosphorylation of AKT at Ser 473"
-
MOTS-c phosphorylates the PTEN C-terminal cluster, stabilising the protein while suppressing its phosphatase activity.
"which stabilizes PTEN, resulting in increased protein abundance but suppressed PTEN phosphatase activity"
-
Absolute muscle masses did not differ between treatment groups; the reported effect required normalisation to body weight.
"Although no differences were found between any of the three treatment groups when considering total, gastrocnemius, soleus, and plantaris absolute muscle mass, differences were more visible when performing an adjustment calculation with body weight."
MOTS-c is a mitochondrial-encoded interferon-linked host defense peptide.
-
MOTS-c is an amphipathic cationic peptide with direct antibacterial activity against E. coli and MRSA, acting on bacterial membranes via its hydrophobic core and cationic tail.
"MOTS-c targeted Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA), in part, by targeting their membranes using its hydrophobic and cationic domains."
-
Endogenous MOTS-c expression is induced in human monocytes by interferon gamma, LPS and differentiation signals.
"In human monocytes, interferon gamma (IFNγ), lipopolysaccharides (LPS), and differentiation signals each induced the expression of endogenous MOTS-c."
-
MOTS-c-programmed macrophages show increased bacterial killing capacity.
"First, MOTS-c-programmed THP-1 macrophages exhibited a significant increase in bacterial killing capacity, determined using a gentamicin protection assay"