Research Peptide · For laboratory research use only
Also known as Mitochondrial ORF of 12S rRNA-c
MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid peptide, MRWQEMGYIFYPRKLR, encoded by a short open reading frame within the mitochondrial 12S rRNA gene. It was reported in 2015 as a mitochondrial-derived peptide, following the earlier identification of humanin1.
Research to date is largely in mice and cell culture, covering metabolic homeostasis and insulin sensitivity, mitonuclear signalling under metabolic stress, physical capacity in ageing mice, T cell regulation in an autoimmune diabetes model, and antibacterial activity1,2,3,4,5.
As described in the research literature
As described in the research literature, the originating study identified skeletal muscle as the apparent primary target organ and reported that MOTS-c inhibits the folate cycle and its tethered de novo purine biosynthesis, leading to AMPK activation1. Under metabolic stress such as glucose restriction, MOTS-c was reported to translocate to the nucleus in an AMPK-dependent manner, regulate genes including those with antioxidant response elements, and interact with stress-responsive transcription factors such as NRF22.
In non-obese diabetic mice, MOTS-c was reported to modulate T cell phenotype and function through T cell receptor and mTORC1 signalling4. A 2026 study described MOTS-c as an amphipathic, cationic host defence peptide with direct activity against Escherichia coli and methicillin-resistant Staphylococcus aureus, and reported that it reprogrammed differentiating mouse monocytes into macrophages with distinct transcriptomic signatures5.
What published studies have examined
The 2015 study examined insulin sensitivity, age-dependent and high-fat-diet-induced insulin resistance, and diet-induced obesity in mice, alongside folate cycle, purine biosynthesis and AMPK signalling in cells1.
Sources [1]
Cell studies examined nuclear translocation of MOTS-c after metabolic stress, its dependence on AMPK, and its regulation of nuclear genes, including NRF2-linked antioxidant response element targets2.
Sources [2]
Physical performance was examined in young, middle-aged and old mice, together with nuclear gene regulation, skeletal muscle metabolism and myoblast adaptation to metabolic stress3.
Sources [3]
In non-obese diabetic mice, studies examined hyperglycaemia, islet-infiltrating immune cells and adoptive T cell transfer into NOD-SCID mice (a correction to this paper was published in 2021)4. Antibacterial activity was examined in vitro and in a mouse model of MRSA peritonitis, and monocyte differentiation in primary mouse cells5.
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.
Lee C, Zeng J, Drew BG, et al. Cell Metabolism, 2015.
The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress.
Kim KH, Son JM, Benayoun BA, et al. Cell Metabolism, 2018.
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis.
Reynolds JC, Lai RW, Woodhead JST, et al. Nature Communications, 2021.
Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes.
Kong BS, Min SH, Lee C, et al. Cell Reports, 2021.
MOTS-c is a mitochondrial-encoded interferon-linked host defense peptide.
Rice MC, Imun M, Jung SW, et al. eLife, 2026.
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.