SS-31 vs MOTS-c: two "mitochondrial peptides" with little in common

You've probably seen SS-31 and MOTS-c in the same post, sometimes in the same sentence, both filed under "mitochondrial peptides". So here's the one-line answer first: they are not related. SS-31 is a four-residue molecule designed by chemists. MOTS-c is a 16-residue peptide that was found, in 2015, written into the DNA inside our own mitochondria. The only thing they share is the organelle researchers study them in.

The rest of this page sets them side by side: where each comes from, how big each is, what makes SS-31's chemistry unusual, how much of the research is in people versus cells, and where each stands with regulators.

Side by side

Masses and formulas are from PubChem. MOTS-c is roughly three and a half times the mass of SS-31.

Where each one comes from

MOTS-c is a natural sequence. Lee and colleagues reported it in Cell Metabolism in 2015 as a 16-amino-acid peptide read from a short open reading frame inside the mitochondrial 12S ribosomal RNA gene. The name spells that out. It belongs to a small group called mitochondrial-derived peptides. We cover it in full in MOTS-c, explained, and alongside KPV in MOTS-c and KPV.

SS-31 was never found in nature. It's one of the Szeto–Schiller peptides, a family named after the researchers Szeto and Schiller. A 2004 paper they co-authored in the Journal of Biological Chemistry describes the family's design: a short chain that alternates aromatic and basic amino acids, with dimethyltyrosine built in. Elamipretide is the international non-proprietary name the same molecule was later given. Older trial registrations use a development code and an earlier name for it; they are the same compound.

One honest aside: "mitochondrial peptide" is a description of where researchers look, not a family. A natural peptide encoded by mitochondrial DNA and a synthetic one designed to reach the mitochondrial membrane end up under the same heading in posts, and that is about all they have in common.

What makes SS-31's chemistry unusual

Most peptides, MOTS-c included, are built only from the standard L-amino acids that cells use to make proteins. SS-31 breaks that rule in three places:

• A D-amino acid at the start. The first residue is D-arginine, the mirror image of the usual L-form.
• Dmt in position two. Dmt stands for 2',6'-dimethyl-L-tyrosine: tyrosine with two extra methyl groups on its ring. It isn't one of the twenty standard amino acids. The 2004 paper reports that versions of the peptide without it behaved differently in its experiments.
• An amidated end. The chain finishes in -NH2 rather than the usual free acid, which changes the charge at that end.

For anyone checking identity on a report, this matters. A mass of about 640 Da on a certificate is a four-residue molecule; about 2,175 Da is a sixteen-residue one. There is no way to mistake one for the other on a mass spectrum. How HPLC-MS confirms purity and identity explains how that check is read.

Where each acts, at the molecular level

This is biochemistry only, as the papers describe it in cells, isolated mitochondria and animal models.

SS-31 and cardiolipin. Cardiolipin is a phospholipid found on the inner mitochondrial membrane, where it helps shape the folds (cristae) of that membrane. Birk and colleagues (Journal of the American Society of Nephrology, 2013) used a fluorescent version of SS-31 to report that it binds cardiolipin with high affinity. Szeto's 2014 review in the British Journal of Pharmacology describes that binding as electrostatic and hydrophobic, and frames SS-31 as a compound that interacts with cardiolipin and, through it, with cytochrome c.

MOTS-c and the folate cycle. The 2015 discovery paper reports, in cells and mice, that MOTS-c's cellular actions inhibit the folate cycle and the purine synthesis tied to it, leading to activation of AMP-activated protein kinase (AMPK), an enzyme that senses a cell's energy state. That AMPK link is also why WADA lists MOTS-c where it does (see below).

So one is studied as a molecule that sits in a membrane lipid layer; the other as a signalling peptide linked to an enzyme pathway. Different targets, different questions.

The evidence, by design

If you've read how to read a peptide study, the first question is always: cells, animals or people? Here the two compounds sit at opposite ends.

MOTS-c is almost entirely pre-clinical. The discovery paper is cells and mice. A search of ClinicalTrials.gov for MOTS-c returns nine records, but most of them only measure natural MOTS-c levels in people taking part in other studies. One registration, NCT07505745, gives MOTS-c itself as the intervention: a phase 2 trial, registered as randomised, parallel-group and quadruple-masked, with 120 participants planned. It was recruiting when we checked, with no results posted.

SS-31 has a long trial record. Searching ClinicalTrials.gov for elamipretide and its older names returns 29 registrations: 8 phase 1, 5 phase 1/2, 10 phase 2, 1 phase 2/3, 3 phase 3, 1 phase 4 and 1 expanded-access programme. The later-stage ones, design only:

"Quadruple-masked" is ClinicalTrials.gov's term for a trial where participants, care providers, investigators and outcome assessors don't know who received what. We list the design only; the registrations and their linked publications are where to read what each trial measured.

Regulatory status

SS-31 (elamipretide). On 19 September 2025 the US Food and Drug Administration announced that it had granted accelerated approval to elamipretide injection for Barth syndrome, a rare inherited mitochondrial disease, in patients weighing at least 30 kg. Accelerated approval is a specific US route: the FDA requires a post-approval randomised, double-blind, placebo-controlled trial to confirm clinical benefit. That approval covers one licensed medicine for one indication. It says nothing about any research-grade material sold as "SS-31".

In the UK, a search of the MHRA products database for elamipretide returned no results when we checked, so we found no UK marketing authorisation. FDA approved, MHRA licensed, or neither explains why a US approval doesn't carry over.

MOTS-c holds no marketing authorisation anywhere.

WADA. The 2026 Prohibited List names MOTS-c under S4.4.1, among activators of AMPK, prohibited at all times. We couldn't find SS-31 or elamipretide named on the list. That doesn't make it permitted: S0 catches pharmacological substances with no current government approval for human therapeutic use, and WADA's classes also reach substances that aren't named. Since elamipretide now has an FDA approval, which class applies is a question for an anti-doping body, not a supplier. Peptides on the WADA list explains how S0 works.

Where Biovanta fits

We supply MOTS-c 40 mg for in-vitro laboratory research, with an independent report per batch. We don't sell SS-31, and this page isn't a lead-in to it. If you're comparing listings for either compound, the identity check is the same: the measured mass on the report should match the molecule on the label, about 2,175 Da for MOTS-c and about 640 Da for SS-31.