MOTS-c vs SS-31: Two Mitochondria-Focused Research Peptides
MOTS-c and SS-31 both appear in mitochondrial research, but they are very different molecules. MOTS-c is a 16-residue peptide encoded in mitochondrial DNA; SS-31 is a designed tetrapeptide with unnatural residues. This post compares where each comes from, its chemistry, and the questions the literature asks.
Research blog: general laboratory-science and literature context. Not medical advice. Sealed Peptides materials are for laboratory research use only, and are not for human or veterinary use.
A natural peptide and a designed one
MOTS-c is a mitochondrial-derived peptide: its 16-residue sequence is encoded by a short open reading frame within the mitochondrial 12S rRNA gene. It was described in 2015 as a peptide found in cells and circulation in mice and humans.
SS-31, also called elamipretide, is a synthetic tetrapeptide from the Szeto-Schiller series. It was designed rather than discovered, and it contains residues not found in natural proteins.
Sequence and size at a glance
- MOTS-c: MRWQEMGYIFYPRKLR, formula C101H152N28O22S2, listed molecular weight 2174.5 Da. Two methionines make oxidation a point to watch.
- SS-31: D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2′,6′-dimethyltyrosine; formula C32H49N9O5, listed molecular weight 639.8 Da (free base). The C-terminus is amidated.
- Difference in scale: MOTS-c is more than three times the mass of SS-31, so the two behave very differently on HPLC and in solution.
What the literature examines
MOTS-c studies in mouse and cell models focus on metabolic signaling, with AMP-activated protein kinase (AMPK) activation and the folate cycle as frequent topics; later work examined its movement to the nucleus under stress.
SS-31 studies focus on the inner mitochondrial membrane, where it associates with the phospholipid cardiolipin. Papers measure membrane structure, reactive oxygen species and electron-transport function in cell and animal models. The MOTS-c and SS-31 research overviews list citations.
Characterization and salt forms
Both are checked by mass spectrometry for identity and by HPLC for purity. SS-31 carries three positive charges, so it is usually isolated as a salt, and the Counter-ion adds to the weighed mass; the counter-ion guide explains why that matters for concentration arithmetic.
For MOTS-c, peaks 16 or 32 Da heavier than expected point to oxidized methionine.
Handling notes
Both are supplied as lyophilized powders and stored sealed and frozen. For solution arithmetic with each listed molecular weight, see the MOTS-c and SS-31 reconstitution calculators.
Terms used in this guide
Related tools and guides
For laboratory research use only. Not for human or veterinary use. This post is general chemistry and literature context and does not describe or endorse any use of Sealed Peptides products.
