SS-31 and MOTS-c are both studied for mitochondrial health, but they work in different ways. SS-31 (elamipretide) is a synthetic peptide that targets the inner mitochondrial membrane (binding cardiolipin) to improve energy production, and is an investigational drug in clinical trials. MOTS-c is a mitochondrial-derived peptide — encoded within mitochondrial DNA — studied as a metabolic, exercise-mimetic signal, mostly in preclinical research.
At a glance
| SS-31 | MOTS-c | |
|---|---|---|
| Type | Synthetic mitochondria-targeting peptide | Mitochondrial-derived peptide |
| Mechanism | Binds cardiolipin to stabilize the inner membrane | Metabolic / exercise-mimetic signaling |
| Development | Investigational drug (clinical trials) | Largely preclinical research chemical |
| FDA status | Not approved (in trials) | Not approved |
| Evidence | Clinical trials with mixed results | Cell and animal studies |
The bottom line
Bottom line: Both center on mitochondria but from different angles. SS-31 is a drug candidate that physically protects the mitochondrial membrane and has reached clinical trials (with mixed results). MOTS-c is an endogenous signaling peptide studied for metabolism and exercise mimicry, still mostly preclinical. Neither is approved, and human benefit is not established for either.
Frequently asked questions
What's the difference between SS-31 and MOTS-c?
SS-31 (elamipretide) is a synthetic peptide that targets the inner mitochondrial membrane to improve energy production and is in clinical trials. MOTS-c is a mitochondrial-derived signaling peptide studied for metabolism, mostly in preclinical research.
Are SS-31 or MOTS-c approved?
Neither is FDA-approved. SS-31 (elamipretide) is an investigational drug that has reached clinical trials with mixed results; MOTS-c is a research compound supported mainly by cell and animal data.
Do they slow aging?
No peptide has been shown to slow human aging in rigorous trials. Both are studied in mitochondrial and metabolic contexts, but human longevity benefits are not established.
References
Combined peer-reviewed sources from both peptide guides. Inclusion is not endorsement.
- Karaa A, Haas R, Goldstein A, et al. Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. Neurology. 2018. Peer-reviewed study
- Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 2014. Peer-reviewed study
- Zhao W, Xu Z, Cao J, et al. Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice. J Neuroinflammation. 2019. Peer-reviewed study
- Zheng H, Ou J, Han H, et al. SS-31@Fer-1 Alleviates ferroptosis in hypoxia/reoxygenation cardiomyocytes via mitochondrial targeting. Biomed Pharmacother. 2025. Peer-reviewed study
- Nie Y, Li J, Zhai X, et al. Elamipretide(SS-31) Attenuates Idiopathic Pulmonary Fibrosis by Inhibiting the Nrf2-Dependent NLRP3 Inflammasome in Macrophages. Antioxidants (Basel). 2023. Peer-reviewed study
- Whitson JA, Martín-Pérez M, Zhang T, et al. Elamipretide (SS-31) treatment attenuates age-associated post-translational modifications of heart proteins. Geroscience. 2021. Peer-reviewed study
- Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015. Peer-reviewed study
- Lee C, Kim KH, Cohen P. MOTS-c: a novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med. 2016. Peer-reviewed study
- Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol (Lausanne). 2023. Peer-reviewed study
- Kong BS, Lee C, Cho YM. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases. Diabetes Metab J. 2023. Peer-reviewed study
- Yin Y, Li Y, Ma B, et al. Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination. Adv Sci (Weinh). 2024. Peer-reviewed study
- Yin Y, Pan Y, He J, et al. The mitochondrial-derived peptide MOTS-c relieves hyperglycemia and insulin resistance in gestational diabetes mellitus. Pharmacol Res. 2022. Peer-reviewed study