MOTS-c vs SS-31 (Elamipretide)
MOTS-c (Mitochondrial-derived peptide) and SS-31 (Elamipretide) (Mitochondria-targeted tetrapeptide) are documented as co-studied in the PeptiDex library. This page puts the two entries side by side on class, molecular weight, half-life, origin, mechanism and studied research areas — every value taken from the entry it belongs to.
Why these two are co-studied
Cross-referenced for research context — not a usage or combination recommendation.
At a glance
| Attribute | MOTS-c | SS-31 (Elamipretide) |
|---|---|---|
| Compound class | Mitochondrial-derived peptide | Mitochondria-targeted tetrapeptide |
| Research category | Metabolic & Mitochondrial | Longevity & Cellular |
| Length (amino acids) | 16 amino acids | 4 amino acids |
| Molecular weight | ~2174 g/mol | 639.8 g/mol (approx.) |
| Half-life | Not documented | Not documented |
| Origin | MOTS-c (Mitochondrial ORF of the 12S rRNA type-c) is a 16-amino-acid mitochondrial-derived peptide encoded within the MT-RNR1 (12S rRNA) region of mitochondrial DNA. It was described in 2015 and is one of a small family of mitochondrial-derived peptides. | SS-31 (elamipretide, also known as MTP-131 or Bendavia) is a synthetic, cell-permeable, mitochondria-targeted tetrapeptide developed from the Szeto-Schiller (SS) family of aromatic-cationic peptides. It is one of the most studied members of that peptide series. |
“Not documented” means the PeptiDex entry records no value for that field. Nothing on this page is estimated, and no figure is carried over from one compound to the other.
How MOTS-c works
MOTS-c is reported to regulate metabolic homeostasis, in part via activation of the AMPK pathway and modulation of the folate-methionine cycle and de novo purine biosynthesis. It has been described to translocate to the nucleus under metabolic stress and influence stress-response gene expression. Preclinical work links it to improved insulin sensitivity and glucose uptake in skeletal muscle; it is also described as exercise-responsive.
How SS-31 (Elamipretide) works
SS-31/elamipretide selectively concentrates in the inner mitochondrial membrane, where it is reported to bind the phospholipid cardiolipin. By associating with cardiolipin, it is proposed to stabilize the structure of the inner membrane and cristae, support electron transport chain organization and efficiency, and reduce excessive reactive oxygen species production. These actions are intended to improve mitochondrial bioenergetics under conditions of mitochondrial dysfunction.
Mechanistic descriptions reflect published research-literature understanding and are quoted from each compound's own entry. Much peptide research is preclinical (in-vitro or animal-model); mechanism in humans may differ and is not established for many compounds.
Where each one appears in the literature
The research contexts each entry documents. Listing a research area is not a claim of efficacy or a therapeutic indication, and the two lists are not scored against each other.
MOTS-c
SS-31 (Elamipretide)
What sets each apart
MOTS-c
Unlike the GH-derived fragments here, MOTS-c is endogenously encoded in the mitochondrial genome and acts as a broad metabolic regulator rather than a targeted lipolytic fragment.
SS-31 (Elamipretide)
SS-31 is a synthetic mitochondria-targeting tetrapeptide that physically localizes to the inner membrane and binds cardiolipin, and unlike most peptides here it has advanced into human clinical trials as elamipretide.
Frequently asked questions
What is MOTS-c and where does it come from?
MOTS-c (Mitochondrial Open-reading-frame of the Twelve-S rRNA type-c) is a 16-amino-acid mitochondrial-derived peptide (MDP) encoded within the 12S rRNA region of mitochondrial DNA, rather than by the nuclear genome. First described in 2015, it is studied as a regulator of metabolic homeostasis. Its sequence and MDP origin make it structurally distinct from most catalog peptides.
What is MOTS-c studied for?
MOTS-c is studied in models of metabolic homeostasis, insulin sensitivity, exercise capacity, and aging. Research reported that MOTS-c levels rise with exercise and that exogenous MOTS-c improved glucose tolerance, insulin sensitivity, and running endurance in aged mice. It is thought to act partly via AMPK-linked metabolic signaling.
How is MOTS-c thought to work mechanistically?
MOTS-c is reported to translocate to the nucleus under metabolic stress and influence adaptive gene-expression programs, and it engages the AMPK pathway and folate/one-carbon metabolism to promote glucose uptake and fatty-acid oxidation. This positions it as a signaling peptide linking mitochondrial state to whole-body metabolism in preclinical models.
What is SS-31 (elamipretide)?
SS-31 (elamipretide, also known by the codes Bendavia and SS-31) is a mitochondria-targeted tetrapeptide, D-Arg-Dmt-Lys-Phe-NH2, that concentrates in the inner mitochondrial membrane by binding cardiolipin. It is studied in models of mitochondrial dysfunction, heart failure, ischemia-reperfusion, and age-related bioenergetic decline.
How does SS-31 target mitochondria?
Its alternating cationic and aromatic residues give it strong affinity for cardiolipin, a phospholipid found almost exclusively on the inner mitochondrial membrane. By binding cardiolipin it is thought to stabilize cristae structure and improve electron-transport efficiency, reducing reactive oxygen species.
What is the sequence and molecular weight of SS-31?
SS-31 is the tetrapeptide D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH2 (D-Arg-Dmt-Lys-Phe-NH2), with molecular formula C32H49N9O5 and a molecular weight of about 639.8 g/mol. The unusual dimethyltyrosine and C-terminal amide are defining features.
Answers are the ones published on each compound's own PeptiDex entry. They are educational summaries of research-literature context and are not medical advice.