One of these peptides is the active ingredient in an FDA-approved drug. The other hasn't had a single published trial that gives it to people. Yet search MOTS-c vs SS-31 and you'll find them lined up as "mitochondrial peptides," like two flavors of the same thing. They aren't.
MOTS-c vs SS-31: a shared label tells you nothing about the evidence
"Mitochondrial" is a topic, not a track record. SS-31 and MOTS-c both involve mitochondria, the tiny power plants inside cells. That's where the similarity ends. One was built in a lab and the other was found in nature, and the research behind them sits at completely different stages. (New to mitochondria? Start with what mitochondrial peptides are.)
The proof: a repair crew and a messenger
Let's get into it.
Picture a factory with its own power plant. SS-31 is the structural engineer who walks into the plant and braces the scaffolding so the generators stay put. MOTS-c is a status report the plant writes itself and sends to head office. Same building. Totally different jobs.
SS-31 was designed in a lab. It's only four building blocks long, and two of them don't show up in ordinary proteins. In 2013, a team at Weill Cornell in New York showed it grabs onto cardiolipin, a fat molecule that works like scaffolding for the energy machinery, and tested it in rat kidneys (Birk et al., JASN 2013).
Then a drug version made it to approval, with misses along the way. On September 19, 2025, the FDA granted accelerated approval to one drug product containing elamipretide, the drug name for SS-31, for Barth syndrome, a rare inherited disease of the mitochondria, in patients weighing at least 30 kg (FDA, 2025). It rests on knee muscle strength as a stand-in measure, so a confirming trial still has to happen. Before that, a 218-person late-stage trial in a mitochondrial muscle disease missed its main goals (Karaa et al., Neurology 2023). And research-grade SS-31 isn't FDA approved.
MOTS-c was found, not built. In 2015, researchers at the University of Southern California found a 16-building-block peptide coded inside the mitochondria's own DNA. In cells and mice, it ended up switching on AMPK, an enzyme that works like the cell's fuel gauge (Lee et al., Cell Metab 2015). In people, a small 2021 study of ten young men found the body's own MOTS-c levels rose briefly with exercise (Reynolds et al., Nat Commun 2021). That measured natural MOTS-c. Nobody added any. The first placebo-controlled trial that gives it to people only started in 2026, and it hasn't reported results (ClinicalTrials.gov).
So why should you care? Because pages mix them up all the time, and an SS-31 trial says nothing about MOTS-c. On our A to E evidence ladder, SS-31 sits at B on the strength of its drug trials. MOTS-c sits at D. Keep the two files separate.
"But didn't the FDA vote on MOTS-c?" An FDA advisory committee recommended it for the pharmacy compounding list in July 2026, even though FDA staff had argued against it (FDA briefing, 2026). That's advice, not an approval.
The big learning lesson
Keep reading: Why mitochondria matter, and the peptides studied with them · What actually happened with the FDA "peptide ban" in 2026
Frequently asked questions
What's the difference between MOTS-c and SS-31?
SS-31 is a lab-designed peptide, four building blocks long, that binds cardiolipin inside mitochondria. MOTS-c is a natural 16-building-block peptide coded in mitochondrial DNA that acts as a signal.
Is SS-31 the same as elamipretide?
Yes. SS-31 is the original research name and elamipretide is its drug name. In 2025 the FDA granted accelerated approval to one elamipretide product for Barth syndrome. Research-grade SS-31 isn't FDA approved.
Is MOTS-c FDA approved?
No. It isn't approved for any use. An FDA advisory committee recommended it for the compounding list in July 2026, but that's advice, not an approval.