Back to Search
Start Over
The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance
- Source :
- Cell Metabolism. 21(3):443-454
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- SummaryMitochondria are known to be functional organelles, but their role as a signaling unit is increasingly being appreciated. The 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. Here we report a sORF within the mitochondrial 12S rRNA encoding a 16-amino-acid peptide named MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) that regulates insulin sensitivity and metabolic homeostasis. 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, leading to 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 actively regulate metabolic homeostasis at the cellular and organismal level via peptides encoded within their genome.
- Subjects :
- Male
Mitochondrial DNA
Mitochondrial-Derived Peptide MOTS-c
Physiology
medicine.medical_treatment
AMP-Activated Protein Kinases
Mitochondrion
Diet, High-Fat
DNA, Mitochondrial
Article
Cell Line
Mice
Insulin resistance
AMP-activated protein kinase
Cell Line, Tumor
medicine
Insulin
Animals
Homeostasis
Humans
Obesity
Muscle, Skeletal
Molecular Biology
Humanin
Mice, Inbred ICR
biology
Cell Biology
medicine.disease
Mitochondria
Mice, Inbred C57BL
Open reading frame
HEK293 Cells
Biochemistry
biology.protein
Insulin Resistance
Peptides
HeLa Cells
Signal Transduction
Subjects
Details
- ISSN :
- 15504131
- Volume :
- 21
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cell Metabolism
- Accession number :
- edsair.doi.dedup.....12776e452db916534a312a7822b3e735
- Full Text :
- https://doi.org/10.1016/j.cmet.2015.02.009