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Molecular Weight
Purity
Storage
Appearance
Solubility
01
MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-residue peptide encoded by a short open reading frame within the mitochondrial 12S ribosomal RNA gene. It was first described in 2015 and is one of the best-studied mitochondrial-derived peptides, a group that also includes humanin.
Research has focused on its links to cellular energy metabolism, particularly the AMPK pathway, the folate cycle and purine synthesis, and on its reported movement into the nucleus under stress. The material here is a synthetic version of the published sequence, supplied as a lyophilized reference compound for in vitro research only.
02
MOTS-c is a short, strongly basic peptide with several sensitive residues.
Sequence
Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg, with free termini.
Charge
Three arginines, one lysine and the N-terminus outweigh one glutamate and the C-terminus, giving a net charge of about +3 at neutral pH and a strongly basic isoelectric point.
Methionines (Met1, Met6)
Two oxidation-sensitive sites, each adding 16 Da when oxidised to the sulfoxide.
Aromatic residues
Trp3, Tyr8, Phe10 and Tyr11 give strong UV absorbance at 280 nm and natural fluorescence. Trp3 can also oxidise.
Basic C-terminus
The Pro-Arg-Lys-Leu-Arg end concentrates positive charge, which affects chromatography and surface adsorption.
03
Published research on MOTS-c spans cell and animal studies.
Folate cycle and AMPK
Studies reported that MOTS-c inhibits the folate cycle and de novo purine synthesis, leading to accumulation of AICAR, an endogenous activator of AMPK. This is proposed as an indirect route to AMPK activation rather than direct kinase binding.
Glucose metabolism
Cell-based experiments measured changes in AMPK phosphorylation, metabolic gene expression and glucose uptake after exposure.
Nuclear translocation
Under metabolic stress, MOTS-c has been reported to move into the nucleus and influence the expression of stress-response genes.
Preclinical context
Animal studies have examined metabolism, exercise capacity and ageing-related outcomes; these are cited only as background.
These findings are cited as research context only; no effects are claimed for this material.
04
AMPK pathway studies
A tool compound in cell assays measuring AMPK phosphorylation by Western blot or ELISA.
Metabolomics
Used in experiments tracking folate-cycle and purine-synthesis intermediates such as AICAR.
Localisation studies
Labelled versions are used in imaging studies of cellular uptake and nuclear translocation.
Oxidation model
With two methionines and a tryptophan, it is a useful substrate for studying site-specific oxidation.
05
Storage
Store the lyophilized powder at −20 °C, sealed, desiccated and protected from light.
Oxidation
Met1 and Met6 oxidise in the presence of oxygen, trace metals and light; Trp3 can also oxidise. Use degassed buffers, minimise headspace or blanket with nitrogen or argon, and consider a chelator such as EDTA to remove trace metals. Avoid adding ascorbate, which can promote oxidation when metals are present.
Light
The aromatic residues are light-sensitive; use amber or foil-wrapped vials.
Reconstitution
Soluble in water and dilute acetic acid.
Labware
Use low-binding polypropylene tubes; the cationic peptide adsorbs to glass at low concentrations. Freeze single-use aliquots and avoid repeated freeze–thaw cycles.
06
MOTS-c is easy to detect but needs careful monitoring of oxidation.
HPLC
Reversed-phase C18 with a TFA gradient. Detect at 214 nm, or at 280 nm for selectivity against non-aromatic components. Oxidised forms are more polar and usually elute earlier.
Mass spectrometry
ESI gives [M+2H]²⁺ and [M+3H]³⁺ ions at about m/z 1087.6 and 725.4 (monoisotopic; about 1088.3 and 725.9 by average mass). MS/MS gives strong y-ions from the arginine-rich C-terminus and immonium ions for tryptophan (m/z 159.1) and tyrosine (m/z 136.1).
Oxidation analysis
Single oxidation adds 16 Da and double oxidation 32 Da. Because Met1, Met6 and Trp3 can all add 16 Da, MS/MS is needed to locate each modification.
Impurity profile
Typical checks include Met and Trp oxidation products, deletion and truncated sequences, and counter-ion content. Acceptance limits for oxidation are set in the lot specification.
07
Mitochondrial open reading frame of the 12S rRNA type-c. It is encoded by a short open reading frame inside the mitochondrial 12S ribosomal RNA gene.
Met1 and Met6 are easily oxidised to methionine sulfoxide (+16 Da each) by oxygen, trace metals and light. Oxidised forms can behave differently in assays, so their levels are monitored.
Mainly AMPK, reported to be activated indirectly through inhibition of the folate cycle and accumulation of AICAR, along with glucose-uptake pathways and stress-related gene expression after nuclear translocation.
Reversed-phase HPLC with UV at 214 nm or, more selectively, 280 nm thanks to its aromatic residues; fluorescence detection; and LC-MS, which also tracks oxidation.
By mass: single oxidation adds 16 Da and double oxidation 32 Da. Single-oxidised forms at Met1, Met6 or Trp3 have the same mass but usually separate by HPLC, and MS/MS locates the modified residue: N-terminal b-ions show Met1 changes, while fragments spanning residues 3–6 distinguish Trp3 from Met6.
No. It is supplied strictly as a reference compound for laboratory and analytical research and is not for human or animal use.
MOTS-c Research Reference. (2026). Pure Peptides Labs Research Catalogue. Retrieved from https://purepeptideslabs.net/research-catalogue/cellular-research-peptides/mots-c/
Materials listed on this platform are supported by independent testing and published documentation for laboratory research contexts.
