MOTS-c vs SS-31: Evidence, Approval and Key Differences

By Editorial team. Updated Oct 15, 2026. Awaiting expert review

MOTS-c and SS-31 are both peptides linked to mitochondria, but they are very different molecules at very different stages of research. MOTS-c is a natural 16-amino-acid peptide encoded in mitochondrial DNA and studied mainly in mice [1, 2]. SS-31 is elamipretide, a synthetic peptide that binds a lipid in the inner mitochondrial membrane; it has been through human trials and received accelerated approval in the US in 2025 for a rare genetic disorder [12, 5, 8].

What each one is

MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a 16-amino-acid peptide encoded by a short open reading frame in the mitochondrial 12S rRNA gene, first described in 2015 [1]. The body makes it: it is found in plasma, and its levels fall with age [2]. Under metabolic stress it moves into the cell nucleus and influences the expression of nuclear genes [2].

SS-31 is elamipretide, a member of the Szeto-Schiller family of peptides that selectively target the inner mitochondrial membrane [5]. Unlike MOTS-c, it is synthetic: a small, positively charged tetrapeptide, four amino acids long [12, 6], that binds cardiolipin, a lipid of the inner mitochondrial membrane [5].

How the evidence compares

For MOTS-c, the key studies are in animals. In mice, MOTS-c treatment prevented diet-induced obesity and age-related insulin resistance, acting mainly on skeletal muscle [1]. A 2023 review notes that MOTS-c has rarely been used in disease treatment and that no effective method of applying it clinically has been developed [2]. FDA has not identified any human exposure data for drug products containing MOTS-c, given by any route [3].

SS-31 (elamipretide) has been through human trials, with mixed results. In September 2025, FDA granted it accelerated approval to improve muscle strength in Barth syndrome, an ultra-rare X-linked genetic disorder [8, 9]. The Barth syndrome data come from few patients: in the open-label extension of the TAZPOWER trial, 10 patients continued treatment and 8 reached 168 weeks, with improvements in walking distance [7]. In a different condition, primary mitochondrial myopathy, the phase 3 MMPOWER-3 trial of 218 people did not meet its primary endpoints for walking distance or fatigue, although the drug was well tolerated [6]. It is also in phase 3 development for dry age-related macular degeneration [8].

A 2026 review of peptides marketed directly to patients, which covered both MOTS-c and SS-31, concluded that rigorous human safety data are scarce for unapproved peptides of this kind [11].

Regulation and sport

FDA has approved elamipretide, under accelerated approval, only to improve muscle strength in adults and children with Barth syndrome who weigh at least 30 kg [8, 9]. As the table above shows, MOTS-c is not approved in any market we track, and WADA bans it in sport at all times [10].

Quality risks when buying

Forzinity, the approved elamipretide product, is a prescription medicine [9]; vials sold online as “SS-31” are not that product, and their identity, purity and sterility are unverified unless independently tested. For MOTS-c, FDA says it has encountered multiple salts and derivatives sold under the name [4], and it flags potential immune reactions (immunogenicity) and complexities with peptide-related impurities and characterization [3]. With no approved MOTS-c product to compare against, independent testing of identity and purity is the only check on what a vial contains.

Our guides explain how to read a peptide COA, how to check a peptide vendor and what “research use only” means.

More on each

The MOTS-c overview and the SS-31 overview list each compound’s full sources. We track current listings on the MOTS-c price page and the SS-31 price page.