- 16
- Amino acids in MOTS-c
- 4
- Amino acids in SS-31
- 2015
- Year MOTS-c was reported
The short answer
What are MOTS-c and SS-31?
MOTS-c and SS-31 are both short peptides, and both are tied to mitochondria. Mitochondria are the small parts inside a cell that make most of its chemical energy. The two peptides are still different kinds of compound.
MOTS-c is a peptide that the cell's own mitochondrial DNA codes for [1]. SS-31 is a four-amino-acid peptide that a lab designed to reach the mitochondria [4].
That split in origin is the most useful thing to know when you see both on a shelf. It decides how each one is named, how long its sequence is, and what a lab report should show.
This page covers what each compound is and what the papers looked at. For laboratory research only. Not for human or veterinary use.
MOTS-c
Where does MOTS-c come from?
Most of a cell's DNA sits in the nucleus. Mitochondria carry a small loop of their own. A 2015 paper in Cell Metabolism reported a short open reading frame inside the mitochondrial 12S rRNA gene [1]. An open reading frame is a stretch of DNA that a cell can read to make a peptide.
That stretch codes for a 16-amino-acid peptide. The authors named it MOTS-c, short for mitochondrial open reading frame of the 12S rRNA-c [1].
The same paper looked at MOTS-c in cells and in mice. The authors reported that skeletal muscle appeared to be its main target organ [1].
A 2018 review in the journal Cells described a later report. In it, MOTS-c moved into the cell nucleus under stress, where it bound DNA and worked with other factors on stress response genes [2].
SS-31
A four-residue peptide built to reach mitochondria
SS-31 is much shorter. Its sequence is D-Arg-Dmt-Lys-Phe-NH2, which is four amino acids [4]. Dmt stands for 2',6'-dimethyltyrosine, a modified form of tyrosine.
The "D" on the first arginine means it is the mirror-image form of the amino acid. The "NH2" at the end is an amide cap on the last residue. Both show up in the written sequence, so a label that leaves them out is missing detail.
SS-31 also goes by the name elamipretide. A 2025 review in the International Journal of Molecular Sciences lists both names for the same tetrapeptide [6].
A 2004 paper in the Journal of Biological Chemistry described the design pattern behind this peptide family. It centers on alternating aromatic and basic amino acids [5].
D-Arg
Arginine in its mirror-image (D) form, at the start of the chain.
Dmt
2',6'-dimethyltyrosine, a modified tyrosine.
Lys
Lysine, an ordinary amino acid.
Phe-NH2
Phenylalanine with an amide cap at the end.
Compare
MOTS-c and SS-31 side by side
The big difference is origin. MOTS-c copies a sequence found in mitochondrial DNA [1]. SS-31 was developed in a lab, using a pattern chosen to concentrate in the inner mitochondrial membrane [5].
Size is the second difference. At 16 amino acids against four, the two have very different masses, so their reports should look different too.
The written sequences differ as well. The 2015 paper describes MOTS-c as a 16-amino-acid peptide. SS-31 packs three special details into four residues: a mirror-image start, a modified tyrosine and an amide cap [1] [4].
| MOTS-c | SS-31 | |
|---|---|---|
| Origin | Coded in mitochondrial DNA | Designed in a lab |
| Length | 16 amino acids | 4 amino acids |
| Other names | Mitochondrial open reading frame of the 12S rRNA-c | Elamipretide |
| Written sequence | 16 residues | D-Arg, Dmt, Lys and Phe-NH2 |
| What papers measured | Where it acts in cells and mice | Where it goes in cells and what it binds |
The studies
What the papers actually measured
Zhao and colleagues tested SS-31 on two neuronal cell lines in 2005. They exposed the cells to an oxidant and measured reactive oxygen species, mitochondrial potential and cell death [4].
They also measured where the peptide ended up. Inside cells it was about six times more concentrated than outside. In isolated mitochondria it was concentrated about 5000-fold [4].
A 2013 paper used a fluorescent copy of SS-31 to measure binding. It found the peptide binds cardiolipin, a lipid on the inner mitochondrial membrane [3]. A 2025 review describes the same binding [6].
For a buyer, the point is how specific these studies are. Each one used a named model, a named measurement and a named version of the peptide. No paper here tested a product from any supplier.
Timeline
How the research unfolded
The SS-31 family came first in this set. The peptide antioxidant design appeared in 2004 [5], and the cardiolipin binding work followed in 2013 [3].
MOTS-c papers start in 2015 [1]. The nucleus report was summarized in a 2018 review [2].
The papers also differ in kind. Some are cell studies, some used isolated mitochondria, some used mice or rats, and two are reviews. That mix is why each claim on this page names its paper.
- 2004
A Journal of Biological Chemistry paper describes cell-permeable peptide antioxidants aimed at the inner mitochondrial membrane.
- 2005
SS-31 is tested in two neuronal cell lines under oxidant exposure.
- 2013
SS-31 is shown by fluorescence to bind cardiolipin.
- 2015
MOTS-c is reported as a 16-amino-acid peptide from the 12S rRNA gene.
- 2018
A review summarizes a report of MOTS-c entering the nucleus under stress.
Before you choose
What should you check on the label and the report?
Start with the name. If the label says SS-31, the report should say SS-31 or elamipretide. The two names mean the same tetrapeptide [6].
Next, check the sequence. SS-31 has a mirror-image residue, a modified residue and an amide cap, so a plain four-letter code leaves out detail. MOTS-c should list 16 residues.
Then read the lab report for that exact product. It should name the lab and show how purity was measured. Our certificate of analysis page shows what a report looks like, and the glossary explains terms like HPLC.
You can compare suppliers with the supplier checklist. For more on each compound, see the MOTS-c and SS-31 pages.
- Name matches the report (SS-31 or elamipretide)
- Sequence matches the length: 16 for MOTS-c, 4 for SS-31
- Report names the lab and the test method
- Report is for this exact product
Questions
Common questions
Is MOTS-c the same as humanin?
No. Humanin was found earlier, and the 2015 MOTS-c paper cites it as an earlier example of a peptide coded in mitochondrial DNA. MOTS-c is a separate 16-amino-acid sequence.
Are SS-31 and elamipretide the same compound?
Yes. A 2025 review lists them as two names for the same tetrapeptide.
How long are MOTS-c and SS-31?
MOTS-c has 16 amino acids. SS-31 has four. The sequence on a report should match.
Why does the SS-31 sequence have a D and an NH2 in it?
The D marks a mirror-image amino acid. The NH2 marks an amide cap at the end. Both are part of the compound's written sequence.