# MOTS-c peptide: The Mitochondrial-Derived Signal, by the Evidence > MOTS-c peptide is a 16-amino-acid signal encoded inside mitochondrial DNA that activates AMPK and improved metabolism and physical capacity in animal studies. A cited literature digest. What the published literature measured — the AMPK mechanism, the aged-mouse performance data, the human biomarker thread — with every quantitative claim cited and every gap labeled. ## The short version The **MOTS-c peptide** is a tiny molecule your own cells make. It is encoded not in the main genome but inside the DNA of the mitochondria — the cell's power plants — and it acts as a chemical message about energy. In mice, giving extra MOTS-c improved blood-sugar handling, blocked diet-driven weight gain, and made even old animals run further on a treadmill. In people, the molecule itself rises with exercise and shifts with age, but no completed human trial has tested injecting it. Everything precise on this page comes from published studies; every place the human evidence stops, we say so. ## What the MOTS-c literature has established MOTS-c was identified in 2015 as a 16-amino-acid peptide (sequence MRWQEMGYIFYPRKLR) encoded by a short open reading frame inside the mitochondrial 12S ribosomal RNA gene, MT-RNR1 [1]. It is one of a small family of mitochondrial-derived peptides — short proteins written into mitochondrial DNA rather than the cell nucleus. Its core action is metabolic. MOTS-c inhibits the folate cycle (the set of reactions a cell uses to build the parts of DNA and to pass around one-carbon chemical tags), which causes the intermediate AICAR to accumulate and activates AMPK — the enzyme a cell uses as its low-fuel sensor [1]. In mice, that pathway translated into measurable outcomes: MOTS-c treatment prevented diet-induced obesity and the insulin resistance that comes with a high-fat diet, with skeletal muscle as the primary target organ [1]. The story is not only metabolic. Exercise raises the body's own MOTS-c, and giving extra MOTS-c improved physical performance in young, middle-aged, and old mice — a result that earned the peptide its description as a candidate exercise mimetic (a molecule that copies some of the molecular changes of physical training) [2]. A separate study showed MOTS-c does something rare for a mitochondrial peptide: under stress it leaves the mitochondria and enters the nucleus to switch genes on and off [3]. The honest counterweight is the human evidence. There are no completed interventional human trials of injected MOTS-c [4]. The human data are observational: the molecule rises with exercise, falls in obese children, and, in one dialysis cohort, tracked with mortality risk [12]. That gap between consumer interest and clinical proof is exactly what this digest exists to map. ## What Is MOTS-c? ### What Is MOTS-c? MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA type-c) is a 16-amino-acid peptide encoded inside the mitochondrial genome, in the MT-RNR1 (12S rRNA) region [1]. Molecular weight is 2174.61 Da; CAS 1627580-64-6; sequence MRWQEMGYIFYPRKLR. It is highly conserved across mammals and is detectable in human plasma and skeletal muscle, where levels are exercise-inducible and change with age [4]. ### What does the MOTS-c peptide do? MOTS-c is a 16-amino-acid mitochondrial-derived peptide that inhibits the folate cycle to activate AMPK and, under stress, translocates to the nucleus to regulate gene expression [1][3]. Its best-characterized effects are on glucose handling and skeletal muscle in animal models; a 2024 study identified casein kinase 2 (CK2) — a constantly-active enzyme that tags other proteins — as a direct binding target [5]. Human evidence remains observational rather than interventional [4]. ## How this site reads the evidence This is a literature digest, not a clinic and not a vendor. Three reading rules run through every page. First, species are labeled. A result in mice is reported as a result in mice. The 0.5-15 mg/kg/day figures throughout the research are rodent intraperitoneal doses [1][2] — animal methodology, never a human instruction. See [how MOTS-c doses are expressed](/dosage) for the full framing. Second, the human thread is kept separate and honest. The strongest human signals are biomarker associations: serum MOTS-c is decreased in obese children [11], and in a dialysis cohort it was independently associated with mortality and cardiovascular events [12]. These are associations, not proof that taking MOTS-c changes outcomes. The aging-and-biomarker work is collected on [MOTS-c and mitochondrial aging](/mitochondrial-aging). Third, the regulatory line is stated plainly. MOTS-c is not an FDA-approved drug and is sold only for laboratory research [4]. The detail — including the FDA 503A compounding framework and where MOTS-c currently sits — is on [MOTS-c legal status](/legal-status). --- A pixel-clean readout of the MOTS-c record — the AMPK mechanism, the aged-mouse data, and the biomarker thread logged to source and tagged confirmed, every missing human datum flagged in plain HUD caution, with no clinic behind the screen and nothing here dispensed or sold.