Research compendium
MOTS-c: research reference
MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA, within the 12S ribosomal RNA region. In preclinical models, it has been described as acting on the folate-purine pathway and AMP-activated protein kinase. It has been investigated in models of mitochondrial metabolism in rodent studies.
Sequence origin and measured compartment
Do not turn a name’s origin into a localization or function claim. Preserve the specific evidence connecting sequence, detection and response.
- Does the work distinguish a proposed sequence, detected peptide and synthesized material?
- Which compartment or model supplies the signal being interpreted?
- Is the functional readout compared with appropriate system controls?
Mechanism described in the literature
The peptide is associated with AMPK regulation in cellular models. Its mitochondrial origin places it among the mitochondrial genome-derived peptides described in preclinical research.
Declared technical information
The purity value is a product-label specification, not an assay result. A batch result can only be asserted from that batch’s certificate.
| Field | Declared value |
|---|---|
| Chemical name | Peptide derived from mitochondrial 12S rRNA |
| Sequence | Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg |
| Molecular formula | Not available |
| Molecular weight | 2174.6 Da |
| CAS number | 1627580-64-6 |
| Physical form | Lyophilized powder |
| Appearance | White to off-white solid |
| Purity specification | Declared in the batch certificate |
| Identity | Declared in the batch certificate |
| Solubility | Soluble in sterile water and bacteriostatic water |
| Storage | −20 °C, protected from light |
| Stability after reconstitution | Keep refrigerated at 2–8 °C and use within the period defined by the laboratory protocol |
Catalog names and search terms
These names help identify the catalog entry. A descriptive label is not evidence of efficacy, and structural identity still requires appropriate documentation.
- 16-amino-acid mitochondrial peptide
- MRWQEMGYIFYPRKLR
Catalog classification
Mitochondrial peptide
Laboratory handling
Reconstitution: Laboratory procedure: allow the closed vial to reach room temperature, disinfect the septum and slowly transfer the diluent against the inner wall of the vial. Do not shake; gently swirl the vial until fully dissolved. Record the volume, diluent and date in the batch log.
Storage: Sealed vial of lyophilized material: store at −20 °C, protected from light and moisture. Avoid repeated freeze-thaw cycles of reconstituted material; aliquot when the experimental design permits.
Personal protective equipment: Handle in a clean work area with a lab coat, nitrile gloves and eye protection. Dispose of vials, tips and sharps according to the laboratory waste procedure.
What has been studied
The foundational 2015 paper combined cell culture and mice, placing folate metabolism and associated de novo purine biosynthesis upstream of AMP-activated protein kinase, AMPK, rather than the reverse (PMID 25738459). It also identified skeletal muscle as the organ where the signal was concentrated.
A second set of experiments measured physical capacity in young, middle-aged and old mice alongside nuclear metabolic and proteostasis genes and myoblast adaptation to metabolic stress (PMID 33473109). That paper contains the primary bibliography’s only human measurement: endogenous peptide expression in muscle and circulation after exercise. This is an endogenous measurement, not an external intervention.
A third study tracked the peptide inside glucose-restricted cells and described an AMPK-dependent compartment change in vitro (PMID 29983246). This places it in stress-response regulation rather than substrate consumption alone and is the finding with the least independent replication in this bibliography. Sources: PMID 25738459; PMID 33473109; PMID 29983246; PMID 36528071; PMID 36233287; PMID 36761202.
Reported exposure profile
No exposure constants are published here for the unchanged peptide: no measured plasma half-life, albumin-bound fraction or identification of degrading peptidases. Available findings are indirect.
The intestinal model supplies the clearest comparison: unchanged peptide produced no appreciable oral response but did after intraperitoneal exposure. An analog carrying a cell-penetrating sequence at its carboxyl terminus through a linker had a longer in vitro half-life than the original peptide (PMID 36528071). This is a relative comparison of two molecules, not a numerical parameter for this reference.
Reviews describe peptide detection in plasma and colocalization with mitochondria in multiple tissues, with circulating concentration declining with age (PMID 36233287, PMID 36761202). Endogenous concentration also changes with exercise (PMID 33473109). None establishes residence time after external exposure. Sources: PMID 36528071; PMID 36233287; PMID 36761202; PMID 33473109.
Origin and development
The molecule is neither a redesigned hormone nor a signaling-protein fragment. Its reading frame exists in the mitochondrial genome, and the synthesized sequence reproduces its encoded peptide. Its name abbreviates mitochondrial open reading frame of the 12S rRNA, type c, coined in the 2015 discovery paper (PMID 25738459).
The search followed the prior characterization of humanin, which had shown that the mitochondrial genome contains short peptide-producing reading frames. That precedent motivated searching the rest of the genome.
Subsequent development has been conceptual rather than pharmaceutical. In 2018, in vitro work showed a mitochondrially encoded factor regulating nuclear gene expression, extending signaling beyond the reverse direction (PMID 29983246). The 2022 review presents it as a later addition to the mitochondrial-peptide family (PMID 36233287). The only molecular engineering here is the cell-penetrating-tail analog developed to address the intestinal barrier in animal models (PMID 36528071). Sources: PMID 25738459; PMID 29983246; PMID 36233287; PMID 36528071.
Comparison with related compounds
There is no other mitochondrial peptide in the catalog. Comparisons with its cellular-category neighbors can concern structure and site of action, not rank.
MOTS-c has sixteen residues and a mass of 2174.6 Da, versus four residues and 390.35 Da for epitalon, three residues and 307.32 Da for glutathione, and 663.43 Da for the nonpeptide NAD+. It lacks copper coordination as in GHK-Cu and AHK-Cu and the D-retro-inverso configuration of FOXO4-DRI.
It is the only catalog sequence encoded outside the nuclear genome, and in vitro literature describes movement into the nucleus (PMID 29983246). Like the declared profiles of epitalon and FOXO4-DRI, its described site of action is not a membrane receptor. That observation does not rank them. Sources: PMID 29983246.
What the literature has not established
There is no clinical trial using the peptide as an intervention in this bibliography. The sole primary human finding measures endogenous peptide after exercise within a predominantly mouse experimental paper (PMID 33473109). The 2023 review records no established clinical application method (PMID 36761202).
Declining concentration with age does not separate cause from consequence (PMID 36233287). These references identify no membrane receptor; described action is intracellular and transcriptional in vitro (PMID 29983246).
Reviews enumerate many age-associated conditions (PMID 36233287, PMID 36761202), while the primary bibliography consists of a few rodent and cell models. In the intestinal model, the oral finding concerned the analog rather than the original molecule (PMID 36528071). Sources: PMID 33473109; PMID 36761202; PMID 36233287; PMID 29983246; PMID 36528071.
Questions and answers
How is MOTS-c supplied?
MOTS-c is supplied in a sealed vial containing the quantity indicated for the selected variant, with its batch identifier printed on the label.
How is MOTS-c stored in the laboratory?
Store the closed vial at −20 °C, protected from light and moisture. See the laboratory handling section of this page for the complete procedure.
Sources
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance — Cell Metab (2015); PMID 25738459; DOI 10.1016/j.cmet.2015.02.009
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance — Cell Metab (2015); PMID 25738459; DOI 10.1016/j.cmet.2015.02.009
- MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis — Nat Commun (2021); PMID 33473109; DOI 10.1038/s41467-020-20790-0
- MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis — Nat Commun (2021); PMID 33473109; DOI 10.1038/s41467-020-20790-0
- MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases — Int J Mol Sci (2022); PMID 36233287; DOI 10.3390/ijms231911991
- MOTS-c, the Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases — Int J Mol Sci (2022); PMID 36233287; DOI 10.3390/ijms231911991
- MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation — Front Endocrinol (Lausanne) (2023); PMID 36761202; DOI 10.3389/fendo.2023.1120533
- MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation — Front Endocrinol (Lausanne) (2023); PMID 36761202; DOI 10.3389/fendo.2023.1120533
- The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. — Cell Metab (2018); PMID 29983246; DOI 10.1016/j.cmet.2018.06.008
- The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. — Cell Metab (2018); PMID 29983246; DOI 10.1016/j.cmet.2018.06.008
- Orally administered MOTS-c analogue ameliorates dextran sulfate sodium-induced colitis by inhibiting inflammation and apoptosis. — Eur J Pharmacol (2023); PMID 36528071; DOI 10.1016/j.ejphar.2022.175469
- Orally administered MOTS-c analogue ameliorates dextran sulfate sodium-induced colitis by inhibiting inflammation and apoptosis. — Eur J Pharmacol (2023); PMID 36528071; DOI 10.1016/j.ejphar.2022.175469