MOTS-c and SS-31 (elamipretide): mitochondrial peptides, evidence and status

Why these two are often grouped

MOTS-c and SS-31 both relate to mitochondria, the energy-producing structures inside cells. Beyond that they are very different. MOTS-c is a peptide naturally encoded by mitochondrial DNA. SS-31 is a synthetic peptide designed to bind the inner mitochondrial membrane.

Their evidence levels are also very different, which is the main point of this article.

MOTS-c: what it is

MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16-amino-acid peptide encoded in the 12S rRNA region of the mitochondrial genome. Under metabolic stress it has been reported to move to the cell nucleus and influence gene expression, and it acts in part through the AMPK pathway.

The landmark 2015 study in Cell Metabolism found that MOTS-c treatment in mice prevented age-dependent and high-fat-diet-induced insulin resistance and diet-induced obesity.

MOTS-c: human evidence and status

Direct human trials of MOTS-c itself are lacking. A modified analogue, CB4211, was tested by CohBar in a Phase 1a/1b study in people with fatty liver disease and obesity, with positive topline results announced in 2021; that does not transfer automatically to unmodified MOTS-c.

MOTS-c is not an approved medicine. In July 2026 an FDA advisory committee voted 7–5, with two abstentions, to recommend it for the US compounding bulks list, which is not an approval. Anti-doping guidance lists MOTS-c as prohibited, so athletes should treat it as a doping risk.

SS-31 (elamipretide): what it is

SS-31, developed as elamipretide by Stealth BioTherapeutics, is a small synthetic peptide that binds cardiolipin, a lipid of the inner mitochondrial membrane. The aim is to stabilise mitochondrial structure and function in diseases where they are impaired.

SS-31: from failed trial to approval

Elamipretide's path was not straightforward. In MMPOWER-3, a Phase 3 trial in primary mitochondrial myopathy, it did not meet its primary endpoints of six-minute walk distance and fatigue, although later analyses suggested possible benefit in a genetic subgroup.

On 19 September 2025 the FDA granted accelerated approval to elamipretide as Forzinity to improve muscle strength in patients with Barth syndrome weighing at least 30 kg. Accelerated approval was based on knee extensor muscle strength, an intermediate endpoint, and continued approval may depend on a confirmatory trial.

That approval covers Forzinity for Barth syndrome. It does not validate SS-31 for general energy, ageing or performance uses, and it does not apply to research material sold under the SS-31 name.