MOTS-c and SS-31 are compared because both are tied to mitochondria. MOTS-c is a peptide encoded in mitochondrial DNA and studied as a metabolic regulator. SS-31, also called elamipretide, is a synthetic four-amino-acid peptide that binds cardiolipin inside mitochondria. In September 2025 the FDA granted SS-31 accelerated approval as Forzinity for Barth syndrome; MOTS-c is not FDA-approved.
At a glance
| MOTS-c | SS-31 (Elamipretide) | |
|---|---|---|
| What it is | Peptide encoded in mitochondrial DNA, studied as a metabolic regulator and sometimes called an exercise mimetic | Mitochondria-targeted tetrapeptide (elamipretide) that binds cardiolipin on the inner mitochondrial membrane |
| How it's thought to work | Studied for moving to the cell nucleus under metabolic stress and activating AMPK signaling, affecting glucose and fat metabolism | Binds cardiolipin, stabilizing the electron transport chain, supporting ATP production and reducing reactive oxygen species |
| Regulatory status | Not FDA-approved for any human use | FDA accelerated approval as Forzinity for Barth syndrome (September 2025), with a confirmatory trial required; not approved for other uses |
| Strength of evidence | Insulin-sensitivity and exercise findings come from animal studies; human research is at an early stage | Approval based on an intermediate endpoint; the phase 3 mitochondrial myopathy trial and a phase 2 dry AMD trial missed their primary endpoints |
| Reported side effects | Injection site reactions; long-term human data is limited | Injection site reactions, the most common effect in trials, described by the FDA as mild to moderate; long-term data is still developing |
| Common vial sizes | 5mg, 10mg | 10mg, 50mg |
| Mixing math example | 10 mg + 2 mL BAC water = 5,000 mcg/mL, 50 mcg per unit | 10 mg + 2 mL BAC water = 5,000 mcg/mL, 50 mcg per unit |
Key differences
MOTS-c is studied for moving to the cell nucleus under metabolic stress and activating AMPK signaling, affecting glucose use and fat metabolism. SS-31 binds cardiolipin in the inner mitochondrial membrane, stabilizing the electron transport chain and reducing reactive oxygen species.
SS-31 is FDA-approved, under accelerated approval, only for Barth syndrome in patients weighing at least 30 kg, and a confirmatory trial is required. MOTS-c is not FDA-approved for any human use.
Injection site reactions were the most common effect of SS-31 in trials. MOTS-c's reported side effects are injection site reactions. Long-term human data is limited for both.
What the research covers
SS-31's Barth syndrome approval rests on improved knee extensor muscle strength, an intermediate endpoint. Elsewhere its results are mixed: the phase 3 MMPOWER-3 trial in primary mitochondrial myopathy and the phase 2 ReCLAIM-2 trial in dry age-related macular degeneration did not meet their primary endpoints. MOTS-c's findings on insulin sensitivity and exercise capacity come from animal studies, and human research is at an early stage.
Sources
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Lee C et al. Cell Metabolism, 2015. Preclinical
- MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Reynolds JC et al. Nature Communications, 2021. Human trial
- FDA Grants Accelerated Approval to First Treatment for Barth Syndrome. U.S. Food and Drug Administration, 2025. Announcement
- FORZINITY (elamipretide) for injection, for subcutaneous use - Prescribing Information. U.S. Food and Drug Administration, 2025. Fda label
- Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial.. Karaa A et al. Neurology, 2023. Human trial
- ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation.. Ehlers JP et al. Ophthalmology Science, 2025. Human trial
Frequently asked questions
What is the difference between MOTS-c and SS-31?
MOTS-c is encoded in mitochondrial DNA and studied for AMPK signaling. SS-31 is a synthetic peptide that binds cardiolipin in mitochondria and is studied for mitochondrial function.
Is SS-31 or MOTS-c FDA-approved?
SS-31 (elamipretide) received FDA accelerated approval as Forzinity for Barth syndrome only. MOTS-c is not FDA-approved.
Is SS-31 the same as elamipretide?
Yes. SS-31 is the research name for elamipretide.
Which has more human research, MOTS-c or SS-31?
SS-31 has more, including a phase 3 trial and the data behind its Barth syndrome approval. MOTS-c human research is at an early stage.
Both entries, plus the calculator
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