One of these peptides is an FDA-approved drug. The other was discovered only in 2015, hiding in a stretch of DNA that scientists thought held nothing but the mitochondria's own parts list. Yet MOTS-c and SS-31 are routinely listed side by side as "mitochondrial peptides," as if they were two versions of the same thing. They do completely different jobs. One is a message the mitochondria send out. The other is a designed molecule that braces the mitochondria from the inside.
For background on what mitochondria are and why they matter, start with Why Mitochondria Matter.
The short answer
SS-31 is a repair crew. MOTS-c is a messenger. SS-31 goes into the mitochondria and helps hold their energy-making machinery in shape. MOTS-c is made by the mitochondria and carries signals about the cell's energy state to the rest of the cell. SS-31 is an approved drug for one rare disease. MOTS-c is still an early-stage research compound.
An analogy that holds up
Picture a cell as a factory and the mitochondria as its power plant.
SS-31 is a structural engineer. It walks into the power plant and braces the scaffolding that holds the generators in place, so they keep running in their correct positions.
MOTS-c is a status report. It is written by the power plant itself and sent to head office, the nucleus, saying, in effect, "fuel is running low, adjust operations." Head office then changes which instructions it sends out.
Both concern the power plant. They work at completely different levels.
Side by side
| SS-31 (elamipretide) | MOTS-c | |
|---|---|---|
| Origin | Designed in a lab (early 2000s) | Made naturally by the body (discovered 2015) |
| Where its code comes from | Not found in nature | Mitochondrial DNA |
| Size | 4 amino acids | 16 amino acids |
| Type of action | Structural: binds and stabilizes | Signaling: sends a message |
| Main target | Cardiolipin in the inner mitochondrial membrane | AMPK (the cell's energy sensor) and gene regulation in the nucleus |
| Human evidence | Controlled clinical trials; approved for Barth syndrome (2025) | Observational only; no published controlled trials |
| Evidence tier | A (for its approved indication) | D |
SS-31 in more detail
SS-31 is named after its inventors, Hazel Szeto and Peter Schiller. It is tiny, only four amino acids, and two of those are modified forms not found in ordinary proteins. Those modifications help it cross into cells and reach the mitochondria.
Once there, it binds to cardiolipin, a fat molecule found almost only in the inner membrane of mitochondria. Cardiolipin acts as scaffolding for the protein complexes that produce energy. In research models, SS-31 binding helps keep those complexes organized, which improves how efficiently they pass electrons along and reduces the amount that "leaks" as damaging reactive molecules.
That mechanism led to its approval. In Barth syndrome, a rare inherited disease, a genetic fault leaves cardiolipin abnormal. In September 2025 the FDA granted accelerated approval to elamipretide, under the name FORZINITY, for that condition. Accelerated approval is based on an intermediate measure, in this case muscle strength, and requires further confirmatory data. Trials in other mitochondrial diseases have produced mixed results, and some did not meet their main goals.
MOTS-c in more detail
MOTS-c was discovered in 2015 by a team at the University of Southern California. The surprise was where its code was found: inside the mitochondria's own small genome, a stretch of DNA long thought to hold nothing but instructions for the power plant's own parts. MOTS-c showed that mitochondria can also produce signals meant for the rest of the cell.
In cell and animal research, MOTS-c activates AMPK, an enzyme that works like a fuel gauge. When energy runs low, AMPK shifts the cell toward conserving and producing energy. Under metabolic stress, MOTS-c has also been observed moving into the nucleus and influencing which genes are active.
In people, observational studies have found that MOTS-c levels in the blood rise during exercise. That is a measurement of the body's own MOTS-c, not a test of added MOTS-c. Controlled human trials have not been published. In July 2026 an FDA advisory committee recommended MOTS-c for the pharmacy compounding list. That vote is advisory and does not change its approval status.
Why they are grouped together, and why that is misleading
Both peptides involve mitochondria, and both became popular around the same time. That is where the similarity ends.
- Different questions. SS-31 research asks whether the power plant's structure can be protected. MOTS-c research asks how the power plant communicates with the rest of the cell.
- Different evidence. One has completed controlled human trials and an FDA approval. The other has not reached that stage.
- Different chemistry. One is a short, engineered molecule with non-natural building blocks. The other is a longer, entirely natural sequence.
Asking which one is "better" is a little like asking whether a structural engineer is better than a status report. They do different jobs.
The takeaway
MOTS-c and SS-31 share a category name and very little else. SS-31 is a designed stabilizer with an approved use in one rare disease. MOTS-c is a natural messenger whose discovery changed how scientists think about mitochondria, and whose human research is still ahead of it.
Frequently asked questions
What is the difference between MOTS-c and SS-31?
SS-31 is a synthetic four-amino-acid peptide that binds cardiolipin inside mitochondria and helps stabilize the energy-producing machinery. MOTS-c is a natural sixteen-amino-acid peptide encoded in mitochondrial DNA that acts as a signal, activating the cell's energy sensor AMPK and influencing gene activity.
Is MOTS-c natural?
Yes. MOTS-c is produced by the body and is encoded in the mitochondria's own DNA. Research material is made synthetically with the same sequence.
Is SS-31 the same as elamipretide?
Yes. SS-31 is the original research name. Elamipretide is its drug name, and FORZINITY is the brand name under which it was approved for Barth syndrome in 2025.
Is MOTS-c FDA approved?
No. MOTS-c has not been approved for any use. An FDA advisory committee recommended it for the compounding list in July 2026, but that recommendation is not binding and is not an approval.
What are the evidence tiers for MOTS-c and SS-31?
On PUŪRA's A–E evidence ladder, SS-31 is tier A for its approved indication, Barth syndrome. MOTS-c is tier D, meaning the research is preclinical with supporting observational human data.